Publications

Abstract

The phoneme detection task is widely used in spoken word recognition research. Alphabetically literate participants, however, are more used to explicit representations of letters than of phonemes. The present study explored whether phoneme detection is sensitive to how target phonemes are, or may be, orthographically realised. Listeners detected the target sounds [b,m,t,f,s,k] in word-initial position in sequences of isolated English words. Response times were faster to the targets [b,m,t], which have consistent word-initial spelling, than to the targets [f,s,k], which are inconsistently spelled, but only when listeners’ attention was drawn to spelling by the presence in the experiment of many irregularly spelled fillers. Within the inconsistent targets [f,s,k], there was no significant difference between responses to targets in words with majority and minority spellings. We conclude that performance in the phoneme detection task is not necessarily sensitive to orthographic effects, but that salient orthographic manipulation can induce such sensitivity.

Abstract

Bisyllabic sequences which could be interpreted as one word or two were produced in sentence contexts by a trained speaker, and syllabic durations measured. Listeners judged whether the bisyllables, excised from context, were one word or two. The proportion of two-word choices correlated positively with measured duration, but only for bisyllables stressed on the second syllable. The results may suggest a limit for listener sensitivity to syllabic lengthening as a word boundary cue.

Abstract

Word blends combine fragments from two words, either in speech errors or when a new word is created. Previous work has demonstrated that in Japanese, such blends preserve moraic structure; in English they do not. A similar effect of moraic structure is observed in perceptual research on segmentation of continuous speech in Japanese; English listeners, by contrast, exploit stress units in segmentation, suggesting that a general rhythmic constraint may underlie both findings. The present study examined whether mis parallel would also hold for word blends. In spontaneous English polysyllabic blends, the source words were significantly more likely to be split before a strong than before a weak (unstressed) syllable, i.e. to be split at a stress unit boundary. In an experiment in which listeners were asked to identify the source words of blends, significantly more correct detections resulted when splits had been made before strong syllables. Word blending, like speech segmentation, appears to be constrained by language rhythm.

Abstract

Phoneme detection is a psycholinguistic task in which listeners' response time to detect the presence of a pre-specified phoneme target is measured. Typically, detection tasks have used consonant targets. This paper reports two experiments in which subjects responded to vowels as phoneme detection targets. In the first experiment, targets occurred in real words, in the second in nonsense words. Response times were long by comparison with consonantal targets. Targets in initial syllables were responded to much more slowly than targets in second syllables. Strong vowels were responded to faster than reduced vowels in real words but not in nonwords. These results suggest that the process of phoneme detection produces different results for vowels and for consonants. We discuss possible explanations for this difference, in particular the possibility of language-specificity.

Abstract

In a 50,000-word corpus of spoken British English the occurrence of words embedded within other words is reported. Within-word embedding in this real speech sample is common, and analogous to the extent of embedding observed in the vocabulary. Imposition of a syllable boundary matching constraint reduces but by no means eliminates spurious embedding. Embedded words are most likely to overlap with the beginning of matrix words, and thus may pose serious problems for speech recognisers.

Abstract

We can describe the position of one item with respect to another using a number of different ‘frames of reference’. For example, I can use a ‘deictic’ frame that involves the speaker’s viewpoint (The chair is on the far side of the room), or an ‘intrinsic’ frame that involves a feature of one of the items (The chair is at the back of the room). Where more than one frame of reference is available in a language, what motivates the speaker’s choice? This elicitation task is designed to explore when and why people select intrinsic frames of reference, and how these choices interact with non-linguistic problem-solving strategies.

Abstract

People automatically chunk ongoing dynamic events into discrete units. This paper investigates whether linguistic structure is a factor in this process. We test the claim that describing an event with a serial verb construction will influence a speaker’s conceptual event structure. The grammar of Avatime (a Kwa language spoken in Ghana)requires its speakers to describe some, but not all, placement events using a serial verb construction which also encodes the preceding taking event. We tested Avatime and English speakers’ recognition memory for putting and taking events. Avatime speakers were more likely to falsely recognize putting and taking events from episodes associated with takeput serial verb constructions than from episodes associated with other constructions. English speakers showed no difference in false recognitions between episode types. This demonstrates that memory for episodes is related to the type of language used; and, moreover, across languages different conceptual representations are formed for the same physical episode, paralleling habitual linguistic practices

Abstract

We present a new transcription mode for the annotation tool ELAN. This mode is designed to speed up the process of creating transcriptions of primary linguistic data (video and/or audio recordings of linguistic behaviour). We survey the basic transcription workflow of some commonly used tools (Transcriber, BlitzScribe, and ELAN) and describe how the new transcription interface improves on these existing implementations. We describe the design of the transcription interface and explore some further possibilities for improvement in the areas of segmentation and computational enrichment of annotations.

Abstract

Mensen groeien op in verschillende omgevingen, met verschillende ervaringen en verschillende talen. Betekent dat ook dat ze verschillend denken? En als er invloed is van taal op denken, hoe ver reikt die dan? Wordt ons denken begrensd door woorden, of is de invloed meer gematigd en kunnen we er soms zelfs aan ontkomen?

Abstract

The widespread occurrence of ideophones, large classes of words specialized in evoking sensory imagery, is little known outside linguistics and anthropology. Ideophones are a common feature in many of the world’s languages but are underdeveloped in English and other Indo-European languages. Here we study the meanings of ideophones in Siwu (a Kwa language from Ghana) using a pile-sorting task. The goal was to uncover the underlying structure of the lexical space and to examine the claimed link between ideophones and perception. We found that Siwu ideophones are principally organized around fine-grained aspects of sensory perception, and map onto salient psychophysical dimensions identified in sensory science. The results ratify ideophones as dedicated sensory vocabulary and underline the relevance of ideophones for research on language and perception.

Abstract

Under what circumstances do languages die? Why has their “mortality rate” increased dramatically in the recent past? What “causes of death” can be identified for historical cases, to what extent are these generalizable, and how can they be captured in an explanatory theory? In pursuing these questions, it becomes apparent that in typical cases of language death various causes tend to interact in multiple ways. Speakers’ attitudes towards their language play a critical role in all of this. Existing categorial taxonomies do not succeed in modeling the complex relationships between these factors. Therefore, an alternative, dimensional approach is called for to more adequately address (and counter) the causes of language death in a given scenario.

Abstract

People often talk about musical pitch in terms of spatial metaphors. In English, for instance, pitches can be high or low, whereas in other languages pitches are described as thick or thin. According to psychophysical studies, metaphors in language can also shape people’s nonlinguistic space-pitch representations. But does language establish mappings between space and pitch in the first place or does it modify preexisting associations? Here we tested 4-month-old Dutch infants’ sensitivity to height-pitch and thickness-pitch mappings in two preferential looking tasks. Dutch infants looked significantly longer at cross-modally congruent stimuli in both experiments, indicating that infants are sensitive to space-pitch associations prior to language. This early presence of space-pitch mappings suggests that these associations do not originate from language. Rather, language may build upon pre-existing mappings and change them gradually via some form of competitive associative learning.

Abstract

This paper summarizes the results of a descriptive syntactic category analysis of child English no which reveals that young children use and represent no as a determiner and negatives like no pen as NPs, contra standard analyses.

Abstract

Overview Since the early nineties, the on-going dramatic loss of the world’s linguistic diversity has gained attention, first by the linguists and increasingly also by the general public. As a response, the new field of language documentation emerged from around 2000 on, starting with the funding initiative ‘Dokumentation Bedrohter Sprachen’ (DoBeS, funded by the Volkswagen foundation, Germany), soon to be followed by others such as the ‘Endangered Languages Documentation Programme’ (ELDP, at SOAS, London), or, in the USA, ‘Electronic Meta-structure for Endangered Languages Documentation’ (EMELD, led by the LinguistList) and ‘Documenting Endangered Languages’ (DEL, by the NSF). From its very beginning, the new field focused on digital technologies not only for recording in audio and video, but also for annotation, lexical databases, corpus building and archiving, among others. This development not just coincides but is intrinsically interconnected with the increasing focus on digital data, technology and methods in all sciences, in particular in the humanities.

Abstract

This contribution explores the potentials of combining corpora of language use data with language description in e-grammars (or digital grammars). We present three directions of ongoing research and discuss the advantages of combining these and similar approaches, arguing that the technological possibilities have barely begun to be explored.

Abstract

This contribution presents “The Language Archive” (TLA), a new unit at the MPI for Psycholinguistics, discussing the current developments in management of scientific data, considering the need for new data research infrastructures. Although several initiatives worldwide in the realm of language resources aim at the integration, preservation and mobilization of research data, the state of such scientific data is still often problematic. Data are often not well organized and archived and not described by metadata ― even unique data such as field-work observational data on endangered languages is still mostly on perishable carriers. New data centres are needed that provide trusted, quality-reviewed, persistent services and suitable tools and that take legal and ethical issues seriously. The CLARIN initiative has established criteria for suitable centres. TLA is in a good position to be one of such centres. It is based on three essential pillars: (1) A data archive; (2) management, access and annotation tools; (3) archiving and software expertise for collaborative projects. The archive hosts mostly observational data on small languages worldwide and language acquisition data, but also data resulting from experiments

Abstract

The Pioneers project seeks to uncover relationships between the Papuan languages of Island Melanesia. One basic way to uncover linguistic relationships, either contact or genetic, is through lexical comparison. We have seen very few shared words between our Papuan languages and any other languages, either Oceanic or Papuan, but most of the words which are shared are shared because they are commonly borrowed from Oceanic languages. This task is aimed at enabling fieldworkers to collect terms for inland bird and tree species. In the past it is has proved very difficult for non-experts to identify plant and bird species, so the task consists of a booklet of colour pictures of some of the more common species, with information on the range and habits of each species, as well as some information on their cultural uses, which should enable better identification. It is intended that fieldworkers will show this book to consultants and use it as an elicitation aid.

Abstract

1. Introduction Speech conveys not only linguistic meaning but also paralinguistic information, such as features of the speaker’s social background, physiology, and emotional state. Linguistic and paralinguistic information is encoded in speech by using largely the same vocal apparatus and both are transmitted simultaneously in the acoustic signal, drawing on a limited set of acoustic cues. How this simultaneous encoding is achieved, how the different types of information are disentangled by the listener, and how much they interfere with one another is presently not well understood. Previous research has highlighted the importance of acoustic source and filter cues for emotion and linguistic encoding respectively, which may suggest that the two types of information are encoded independently of each other. However, those lines of investigation have been almost completely disconnected (Murray & Arnott, 1993).

Abstract

Definition Perceptual learning in speech describes a change in the mapping from acoustic cues in the speech signal to abstract linguistic representations. Learning leads to a lasting benefit to the listener by improving speech comprehension. The change can occur as a response to a specific feature (such as a talker- or accent idiosyncrasy) or to a global degradation of the signal (such as in synthesized or compressed speech). In perceptual learning, a top-down process is involved in causing the change, whereas purely bottom-up, signal-driven phenomena are considered to be adaptation.

Abstract

Language resource centers allow researchers to reliably deposit their structured data together with associated meta data and run services operating on this deposited data. We are looking into possibilities to create long-term persistency of both the deposited data and the services operating on this data. Challenges, both technical and non-technical, that need to be solved are the need to replicate more than just the data, proper identification of the digital objects in a distributed environment by making use of persistent identifiers and the set-up of a proper authentication and authorization domain including the management of the authorization information on the digital objects. We acknowledge the investment that most language resource centers have made in their current infrastructure. Therefore one of the most important requirements is the loose coupling with existing infrastructures without the need to make many changes. This shift from a single language resource center into a federated environment of many language resource centers is discussed in the context of a real world center: The Language Archive supported by the Max Planck Institute for Psycholinguistics.

Abstract

This Field Manual entry has been superceded by the 2007 version:
https://doi.org/10.17617/2.468728

Abstract

This Field Manual entry has been superceded by the 2007 version: https://doi.org/10.17617/2.468724

Abstract

In this paper we investigate the neural correlates of syntactic classification of an acquired grammatical sequence structure in an event-related FMRI study. During acquisition, participants were engaged in an implicit short-term memory task without performance feedback. We manipulated the statistical frequency-based and rule-based characteristics of the classification stimuli independently in order to investigate their role in artificial grammar acquisition. The participants performed reliably above chance on the classification task. We observed a partly overlapping corticostriatal processing network activated by both manipulations including inferior prefrontal, cingulate, inferior parietal regions, and the caudate nucleus. More specifically, the left inferior frontal BA 45 and the caudate nucleus were sensitive to syntactic violations and endorsement, respectively. In contrast, these structures were insensitive to the frequency-based manipulation.

Abstract

Turn on your affective system by tweaking your face muscles - or getting an eyeful of someone else doing the same.

Abstract

Find the fire that's cooking your memory systems.

Abstract

Emotions are powerful on the inside but often displayed in subtle ways on the outside. Are these displays culturally dependent or universal?

Abstract

In many languages the future is in front and the past behind, but in some cultures (like Aymara) the past is in front. Is it possible to find this mapping as an alternative conceptualization of time in other cultures? If so, what are the factors that affect its choice out of the set of available alternatives? In a paper and pencil task, participants placed future or past events either in front or behind a character (a schematic head viewed from above). A sample of 24 Islamic participants (whose language also places the future in front and the past behind) tended to locate the past event in the front box more often than Spanish participants. This result might be due to the greater cultural value assigned to tradition in Islamic culture. The same pattern was found in a sample of Spanish elders (N = 58), what may support that conclusion. Alternatively, the crucial factor may be the amount of attention paid to the past. In a final study, young Spanish adults (N = 200) who had just answered a set of questions about their past showed the past-in-front pattern, whereas questions about their future exacerbated the future-in-front pattern. Thus, the attentional explanation was supported: attended events are mapped to front space in agreement with the experiential connection between attending and seeing. When attention is paid to the past, it tends to occupy the front location in spite of available alternative mappings in the language-culture.

Abstract

This paper investigates the lexical semantics and relative distributions of verbs describing putting and taking events in Kuuk Thaayorre, a Pama-Nyungan language of Cape York (Australia). Thaayorre put/take verbs can be subcategorised according to whether they may combine with an NP encoding a goal, an NP encoding a source, or both. Goal NPs are far more frequent in natural discourse: initial analysis shows 85% of goal-oriented verb tokens to be accompanied by a goal NP, while only 31% of source-oriented verb tokens were accompanied by a source. This finding adds weight to Ikegami’s (1987) assertion of the conceptual primacy of goals over sources, reflected in a cross-linguistic dissymmetry whereby goal-marking is less marked and more widely used than source-marking.

Abstract

Print Friendly XML Gebre, Binyam Gebrekidan, Max Planck Institute for Psycholinguistics, The Netherlands, binyamgebrekidan.gebre [at] mpi.nl Wittenburg, Peter, Max Planck Institute for Psycholinguistics, The Netherlands, peter.wittenburg [at] mpi.nl Introduction Many gesture and sign language researchers manually annotate video recordings to systematically categorize, analyze and explain their observations. The number and kinds of annotations are so diverse and unpredictable that any attempt at developing non-adaptive automatic annotation systems is usually less effective. The trend in the literature has been to develop models that work for average users and for average scenarios. This approach has three main disadvantages. First, it is impossible to know beforehand all the patterns that could be of interest to all researchers. Second, it is practically impossible to find enough training examples for all patterns. Third, it is currently impossible to learn a model that is robustly applicable across all video quality-recording variations.

Abstract

Automatic annotation of gesture strokes is important for many gesture and sign language researchers. The unpredictable diversity of human gestures and video recording conditions require that we adopt a more adaptive case-by-case annotation model. In this paper, we present a work-in progress annotation model that allows a user to a) track hands/face b) extract features c) distinguish strokes from non-strokes. The hands/face tracking is done with color matching algorithms and is initialized by the user. The initialization process is supported with immediate visual feedback. Sliders are also provided to support a user-friendly adjustment of skin color ranges. After successful initialization, features related to positions, orientations and speeds of tracked hands/face are extracted using unique identifiable features (corners) from a window of frames and are used for training a learning algorithm. Our preliminary results for stroke detection under non-ideal video conditions are promising and show the potential applicability of our methodology.

Abstract

Recognizing the speech acts in our interlocutors’ utterances is a crucial prerequisite for conversation. However, it is not a trivial task given that the form and content of utterances is frequently underspecified for this level of meaning. In the present study we investigate participants’ competence in categorizing speech acts in such action-underspecific sentences and explore the time-course of speech act inferencing using a self-paced reading paradigm. The results demonstrate that participants are able to categorize the speech acts with very high accuracy, based on limited context and without any prosodic information. Furthermore, the results show that the exact same sentence is processed differently depending on the speech act it performs, with reading times starting to differ already at the first word. These results indicate that participants are very good at “getting” the speech acts, opening up a new arena for experimental research on action recognition in conversation.

Abstract

This paper explores the linguistic encoding of placement and removal events in Swedish. Drawing on elicited spoken data, it provides a unified approach to caused motion descriptions. The results show uniform syntactic behaviour of placement and removal descriptions and a consistent asymmetry between placement and removal in the semantic specificity of verbs. The results also reveal three further semantic patterns, pertaining to the nature of the relationship between Figure and Ground, that appear to account for how these event types are characterised, viz. whether the Ground is represented by a body part of the Agent; whether the Figure is contained within the Ground; or whether it is supported by the Ground.

Abstract

The standard for the analysis of distorted voices is perceptual rating of read-out texts or spontaneous speech. Automatic voice evaluation, however, is usually done on stable sections of sustained vowels. In this paper, text-based and established vowel-based analysis are compared with respect to their ability to measure hoarseness and its subclasses. 73 hoarse patients (48.3±16.8 years) uttered the vowel /e/ and read the German version of the text “The North Wind and the Sun”. Five speech therapists and physicians rated roughness, breathiness, and hoarseness according to the German RBH evaluation scheme. The best human-machine correlations were obtained for measures based on the Cepstral Peak Prominence (CPP; up to |r | = 0.73). Support Vector Regression (SVR) on CPP-based measures and prosodic features improved the results further to r ≈0.8 and confirmed that automatic voice evaluation should be performed on a text recording.

Abstract

We review data and hypotheses dealing with the mental representations for perceived and produced speech that infants build and use over the course of learning a language. In the early stages of speech perception and vocal production, before the emergence of a receptive or a productive lexicon, the dominant picture emerging from the literature suggests rather non-analytic representations based on units of the size of the syllable: Young children seem to parse speech into syllable-sized units in spite of their ability to detect sound equivalence based on shared phonetic features. Once a productive lexicon has emerged, word form representations are initially rather underspecified phonetically but gradually become more specified with lexical growth, up to the phoneme level. The situation is different for the receptive lexicon, in which phonetic specification for consonants and vowels seem to follow different developmental paths. Consonants in stressed syllables are somewhat well specified already at the first signs of a receptive lexicon, and become even better specified with lexical growth. Vowels seem to follow a different developmental path, with increasing flexibility throughout lexical development. Thus, children come to exhibit a consonant vowel asymmetry in lexical representations, which is clear in adult representations.

Abstract

Originally published in Diachronica 27:2 (2010) One attempt at explaining why some language families are large (while others are small) is the hypothesis that the families that are now large became large because their ancestral speakers had a technological advantage, most often agriculture. Variants of this idea are referred to as the Language Farming Dispersal Hypothesis. Previously, detailed language family studies have uncovered various supporting examples and counterexamples to this idea. In the present paper I weigh the evidence from ALL attested language families. For each family, I use the number of member languages as a measure of cardinal size, member language coordinates to measure geospatial size and ethnographic evidence to assess subsistence status. This data shows that, although agricultural families tend to be larger in cardinal size, their size is hardly due to the simple presence of farming. If farming were responsible for language family expansions, we would expect a greater east-west geospatial spread of large families than is actually observed. The data, however, is compatible with weaker versions of the farming dispersal hypothesis as well with models where large families acquire farming because of their size, rather than the other way around.

Abstract

This study investigated whether a shadowing task can provide insights in the nature of reduction processes that are typical of casual speech. We focused on the shortening and presence versus absence of schwa and /t/ in Dutch past participles. Results showed that the absence of these segments was affected by the same variables as their shortening, suggesting that absence mostly resulted from extreme gradient shortening. This contrasts with results based on recordings of spontaneous conversations. We hypothesize that this difference is due to non-casual fast speech elicited by a shadowing task.

Abstract

Co-speech gestures are an integral part of human face-to-face communication, but little is known about how pragmatic factors influence our comprehension of those gestures. The present study investigates how different types of recipients process iconic gestures in a triadic communicative situation. Participants (N = 32) took on the role of one of two recipients in a triad and were presented with 160 video clips of an actor speaking, or speaking and gesturing. Crucially, the actor’s eye gaze was manipulated in that she alternated her gaze between the two recipients. Participants thus perceived some messages in the role of addressed recipient and some in the role of unaddressed recipient. In these roles, participants were asked to make judgements concerning the speaker’s messages. Their reaction times showed that unaddressed recipients did comprehend speaker’s gestures differently to addressees. The findings are discussed with respect to automatic and controlled processes involved in gesture comprehension.

Abstract

This paper examines how placement and removal events are lexicalised and conceptualised in Basque and Peninsular Spanish. After a brief description of the main linguistic devices employed for the coding of these types of events, the paper discusses how speakers of the two languages choose to talk about these events. Finally, the paper focuses on two aspects that seem to be crucial in the description of these events (1) the role of force dynamics: both languages distinguish between different degrees of force, causality, and intentionality, and (2) the influence of the verb-framed lexicalisation pattern. Data come from six Basque and ten Peninsular Spanish native speakers.

Abstract

This paper presents a meta-analysis of hemodynamic studies on passive auditory language processing. We assess the overlap of hemodynamic activation areas and activation maxima reported in experiments involving the presentation of sentences, words, pseudowords, or sublexical or non-linguistic auditory stimuli. Areas that have been reliably replicated are identified. The results of the meta-analysis are compared to electrophysiological, magnetencephalic (MEG), and clinical findings. It is concluded that auditory language input is processed in a left posterior frontal and bilateral temporal cortical network. Within this network, no processing leve l is related to a single cortical area. The temporal lobes seem to differ with respect to their involvement in post-lexical processing, in that the left temporal lobe has greater involvement than the right, and also in the degree of anatomical specialization for phonological, lexical, and sentence -level processing, with greater overlap on the right contrasting with a higher degree of differentiation on the left.

Abstract

Spanish can use dative as well as non-dative strategies to encode Possessors, Human Sources, Interestees (datives of interest) and Experiencers. In Dutch this optionality is virtually absent, restricting dative encoding mainly to the Recipient of a ditransitive. The present study examines whether this may lead to instability of the non-prototypical dative constructions in the Spanish of Dutch-Spanish bilinguals. Elicited data of 12 Chilean heritage informants from the Netherlands were analyzed. Whereas the evidence on the stability of dative Experiencers was not conclusive, the results indicate that the use of prototypical datives, dative External Possessors, dative Human Sources and datives of interest is fairly stable in bilinguals, except for those with limited childhood exposure to Spanish. It is argued that the consistent preference for non-dative strategies of this group was primarily attributable to instability of the dative clitic, which affected all constructions, even the encoding of prototypical indirect objects

Abstract

This study explores the expression of Source and Goal in describing placement and removal events in adult Japanese. Although placement and removal events a priori represent symmetry regarding the orientation of motion, their (c)overt expressions actually exhibit multiple asymmetries at various structural levels. The results show that the expression of the Source is less frequent than the expression of the Goal, but, if expressed, morphosyntactically more complex, suggesting that ‘taking’ events are more complex than ‘putting’ events in their construal. It is stressed that finer linguistic analysis is necessary before explaining linguistic asymmetries in terms of non-linguistic foundations of spatial language.

Abstract

This study investigates the time-course of information processing in both visual as well as in the auditory speech as used for word identification in face-to-face communication. It extends the limited previous research on this topic and provides a valuable database for future research in audiovisual speech perception. An evaluation of models of speech perception by ear and eye in their ability to account for the audiovisual gating data shows a superior role of the fuzzy logical model of perception (FLMP) [1] over additive models of perception. A new dynamic version of the FLMP seems to be a promising model to account for the complex interplay of perceptual and cognitive information in audiovisual spoken word recognition.

Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2–7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active at a low level. Transfection of human glioma cells with the de2-7 EGFR has little effect in vitro, but when grown as tumor xenografts this mutated receptor imparts a dramatic growth advantage. We have now mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies unique to the different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed both in vitro and in vivo, including tyrosine 845, a known target in the wild-type EGFR for src kinase. There was a substantial upregulation of phosphorylation at every tyrosine residue of the de2-7 EGFR when cells were grown in vivo compared to the receptor isolated from cells cultured in vitro. Upregulation of phosphorylation could be mimicked in vitro by the addition of specifi c components of the ECM such as collagen via an integrin-dependent mechanism. Since this increase in in vivo phosphorylation enhances de2-7 EGFR signaling, this observation explains why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment. In a second set of experiments we analyzed the interaction between EGFRvIII and ErbB2. Co-expression of these proteins in NR6 cells, a mouse fi broblast line devoid of ErbB family members, dramatically enhanced in vivo tumorigenicity of these cells compared to cells expressing either protein alone. Detailed analysis of these xenografts demonstrated that EGFRvIII could heterodimerize and transphosphorylate the ErbB2. Since both EGFRvIII and ErbB2 are commonly expressed at gliomas, this data suggests that the co-expression of these two proteins may enhance glioma tumorigenicity.

Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2-7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active at a low level. Transfection of human glioma cells with the de2-7 EGFR has little effect in vitro, but when grown as tumor xenografts this mutated receptor imparts a dramatic growth advantage. We mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies specific for different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed in vitro and in vivo, including tyrosine 845, a known target in the wild-type EGFR for src kinase. There was a substantial upregulation of phosphorylation at every yrosine residue of the de2-7 EGFR when cells were grown in vivo compared to the receptor isolated from cells cultured in vitro. Upregulation of phosphorylation at tyrosine 845 could be stimulated in vitro by the addition of specific components of the ECM via an integrindependent mechanism. These observations may partially explain why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment