Publications

Abstract

Simulations explored the inability of the TRACE model of spoken-word recognition to model the effects on human listening of acoustic-phonetic mismatches in word forms. The source of TRACE's failure lay not in its interactive connectivity, not in the presence of interword competition, and not in the use of phonemic representations, but in the need for continuously optimised interpretation of the input. When an analogue of TRACE was allowed to cycle to asymptote on every slice of input, an acceptable simulation of the subcategorical mismatch data was achieved. Even then, however, the simulation was not as close as that produced by the Merge model.

Abstract

Vocabularies contain hundreds of thousands of words built from only a handful of phonemes, so that inevitably longer words tend to contain shorter ones. In many languages (but not all) such embedded words occur more often word-initially than word-finally, and this asymmetry, if present, has farreaching consequences for spoken-word recognition. Prior research had ascribed the asymmetry to suffixing or to effects of stress (in particular, final syllables containing the vowel schwa). Analyses of the standard French vocabulary here reveal an effect of suffixing, as predicted by this account, and further analyses of an artificial variety of French reveal that extensive final schwa has an independent and additive effect in promoting the embedding asymmetry.

Abstract

Different linguistic structures allow us to highlight distinct aspects of a situation. The aim of this survey is to investigate similarities and differences in the expression of situations or events as “stative” (maintaining a state), “inchoative” (adopting a state) and “agentive” (causing something to be in a state). The questionnaire focuses on the encoding of stative, inchoative and agentive possibilities for the translation equivalents of a set of English verbs.

Abstract

Expressions of human activities and states are a rich area for cross-linguistic comparison. Some languages of the world treat human posture verbs (e.g., sit, lie, kneel) as a special class of predicates, with distinct formal properties. This survey examines lexical, semantic and grammatical patterns for posture verbs, with special reference to contrasts between “stative” (maintaining a posture), “inchoative” (adopting a posture), and “agentive” (causing something to adopt a posture) constructions. The enquiry is thematically linked to the more general questionnaire 'Intransitive Predicate Form Class Survey'.

Abstract

This chapter argues that an evolutionary cultural approach to language not only has already proven fruitful, but it probably holds the key to understand many puzzling aspects of language, its change and origins. The chapter begins by highlighting several still common misconceptions about language that might seem to call into question a cultural evolutionary approach. It explores the antiquity of language and sketches a general evolutionary approach discussing the aspects of function, fi tness, replication, and selection, as well the relevant units of linguistic evolution. In this context, the chapter looks at some fundamental aspects of linguistic diversity such as the nature of the design space, the mechanisms generating it, and the shape and fabric of language. Given that biology is another evolutionary system, its complex coevolution with language needs to be understood in order to have a proper theory of language. Throughout the chapter, various challenges are identifi ed and discussed, sketching promising directions for future research. The chapter ends by listing the necessary data, methods, and theoretical developments required for a grounded evolutionary approach to language.

Abstract

The complex inter-relationships between genetics and linguistics encompass all four scales highlighted by the contributions to this book and, together with cultural transmission, the genetics of language holds the promise to offer a unitary understanding of this fascinating phenomenon. There are inter-individual differences in genetic makeup which contribute to the obvious fact that we are not identical in the way we understand and use language and, by studying them, we will be able to both better treat and enhance ourselves. There are correlations between the genetic configuration of human groups and their languages, reflecting the historical processes shaping them, and there also seem to exist genes which can influence some characteristics of language, biasing it towards or against certain states by altering the way language is transmitted across generations. Besides the joys of pure knowledge, the understanding of these three aspects of genetics relevant to language will potentially trigger advances in medicine, linguistics, psychology or the understanding of our own past and, last but not least, a profound change in the way we regard one of the emblems of being human: our capacity for language.

Abstract

Words evolve not as blobs of ink on paper but in face to face interaction. The nature of language as fundamentally interactive and multimodal is shown by the study of ideophones, vivid sensory words that thrive in conversations around the world. The ways in which these Lautbilder enable precise communication about sensory knowledge has for the first time been studied in detail. It turns out that we can paint with language, and that the onomatopoeia we sometimes classify as childish might be a subset of a much richer toolkit for depiction in speech, available to us all.

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

Spatial congruity effects have often been interpreted as evidence for metaphorical thinking, but an alternative markedness-based account challenges this view. In two experiments, we directly compared metaphor and markedness explanations for spatial congruity effects, using musical pitch as a testbed. English speakers who talk about pitch in terms of spatial height were tested in speeded space-pitch compatibility tasks. To determine whether space-pitch congruency effects could be elicited by any marked spatial continuum, participants were asked to classify high- and low-frequency pitches as 'high' and 'low' or as 'front' and 'back' (both pairs of terms constitute cases of marked continuums). We found congruency effects in high/low conditions but not in front/back conditions, indicating that markedness is not sufficient to account for congruity effects (Experiment 1). A second experiment showed that congruency effects were specific to spatial words that cued a vertical schema (tall/short), and that congruity effects were not an artifact of polysemy (e.g., 'high' referring both to space and pitch). Together, these results suggest that congruency effects reveal metaphorical uses of spatial schemas, not markedness effects.

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

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

In recent years, large scale initiatives like CLARIN set out to overcome the notorious heterogeneity of metadata formats in the domain of language resource. The CLARIN Component Metadata Infrastructure established means for flexible resouce descriptions for the domain of language resources. The Data Category Registry ISOcat and the accompanying Relation Registry foster semantic interoperability within the growing heterogeneous collection of metadata records. This paper describes the CMD Infrastructure focusing on the facilities for semantic mapping, and gives also an overview of the current status in the joint component metadata domain.

Abstract

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

Abstract

Introduction

A comparison of conversation in twenty-one languages from around the world reveals commonalities and differences in the way that people do open-class other-initiation of repair (Schegloff, Jefferson, and Sacks, 1977; Drew, 1997). We find that speakers of all of the spoken languages in the sample make use of a primary interjection strategy (in English it is Huh?), where the phonetic form of the interjection is strikingly similar across the languages: a monosyllable featuring an open non-back vowel [a, æ, ə, ʌ], often nasalized, usually with rising intonation and sometimes an [h-] onset. We also find that most of the languages have another strategy for open-class other-initiation of repair, namely the use of a question word (usually “what”). Here we find significantly more variation across the languages. The phonetic form of the question word involved is completely different from language to language: e.g., English [wɑt] versus Cha'palaa [ti] versus Duna [aki]. Furthermore, the grammatical structure in which the repair-initiating question word can or must be expressed varies within and across languages. In this chapter we present data on these two strategies – primary interjections like Huh? and question words like What? – with discussion of possible reasons for the similarities and differences across the languages. We explore some implications for the notion of repair as a system, in the context of research on the typology of language use.

The general outline of this chapter is as follows. We first discuss repair as a system across languages and then introduce the focus of the chapter: open-class other-initiation of repair. A discussion of the main findings follows, where we identify two alternative strategies in the data: an interjection strategy (Huh?) and a question word strategy (What?). Formal features and possible motivations are discussed for the interjection strategy and the question word strategy in order. A final section discusses bodily behavior including posture, eyebrow movements and eye gaze, both in spoken languages and in a sign language.

Abstract

This chapter contains sections titled: Introduction Lexical Selection in Reference: Introductory Examples of Reference to Times Multiple “Preferences” Future Directions Conclusion

Abstract

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

Abstract

The ethnographic literature has sometimes described parts of the northwest Amazon as areas of shared culture across linguistic groups. This paper illustrates how a principle of semantic transparency across languages is a key means of establishing elements of a common regional culture through practices like the calquing of ethnonyms and toponyms so that they are semantically, but not phonologically, equivalent across languages. It places the upper Rio Negro area of the northwest Amazon in a general discussion of cross-linguistic naming practices in South America and considers the extent to which a preference for semantic transparency can be linked to cases of widespread cultural ‘calquing’, in which culturally-important meanings are kept similar across different linguistic systems. It also addresses the principle of semantic transparency beyond specific referential phrases and into larger discourse structures. It concludes that an attention to semiotic practices in multilingual settings can provide new and more complex ways of thinking about the idea of shared culture.

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

We propose a Random-Forest based sign language identification system. The system uses low-level visual features and is based on the hypothesis that sign languages have varying distributions of phonemes (hand-shapes, locations and movements). We evaluated the system on two sign languages -- British SL and Greek SL, both taken from a publicly available corpus, called Dicta Sign Corpus. Achieved average F1 scores are about 95% - indicating that sign languages can be identified with high accuracy using only low-level visual features.

Abstract

We present a vision-based method for signer diarization -- the task of automatically determining "who signed when?" in a video. This task has similar motivations and applications as speaker diarization but has received little attention in the literature. In this paper, we motivate the problem and propose a method for solving it. The method is based on the hypothesis that signers make more movements than their interlocutors. Experiments on four videos (a total of 1.4 hours and each consisting of two signers) show the applicability of the method. The best diarization error rate (DER) obtained is 0.16.

Abstract

This paper presents a Native Language Identification (NLI) system based on TF-IDF weighting schemes and using linear classifiers - support vector machines, logistic regressions and perceptrons. The system was one of the participants of the 2013 NLI Shared Task in the closed-training track, achieving 0.814 overall accuracy for a set of 11 native languages. This accuracy was only 2.2 percentage points lower than the winner's performance. Furthermore, with subsequent evaluations using 10-fold cross-validation (as given by the organizers) on the combined training and development data, the best average accuracy obtained is 0.8455 and the features that contributed to this accuracy are the TF-IDF of the combined unigrams and bigrams of words.

Abstract

We present and solve the speaker diarization problem in a novel way. We hypothesize that the gesturer is the speaker and that identifying the gesturer can be taken as identifying the active speaker. We provide evidence in support of the hypothesis from gesture literature and audio-visual synchrony studies. We also present a vision-only diarization algorithm that relies on gestures (i.e. upper body movements). Experiments carried out on 8.9 hours of a publicly available dataset (the AMI meeting data) show that diarization error rates as low as 15% can be achieved.

Abstract

How are space and time related in the brain? This study contrasts two proposals that make different predictions about the interaction between spatial and temporal magnitudes. Whereas ATOM implies that space and time are symmetrically related, Metaphor Theory claims they are asymmetrically related. Here we investigated whether space and time activate the same neural structures in the inferior parietal cortex (IPC) and whether the activation is symmetric or asymmetric across domains. We measured participants’ neural activity while they made temporal and spatial judgments on the same visual stimuli. The behavioral results replicated earlier observations of a space-time asymmetry: Temporal judgments were more strongly influenced by irrelevant spatial information than vice versa. The BOLD fMRI data indicated that space and time activated overlapping clusters in the IPC and that, consistent with Metaphor Theory, this activation was asymmetric: The shared region of IPC was activated more strongly during temporal judgments than during spatial judgments. We consider three possible interpretations of this neural asymmetry, based on 3 possible functions of IPC.

Abstract

The shape of pitch contours has been shown to have an effect on the perceived duration of vowels. For instance, vowels with high level pitch and vowels with falling contours sound longer than vowels with low level pitch. Depending on whether the
comparison is between level pitches or between level and dynamic contours, these findings have been interpreted in two ways. For inter-level comparisons, where the duration results are the reverse of production results, a hypercorrection strategy in production has been proposed [1]. By contrast, for comparisons between level pitches and dynamic contours, the
longer production data for dynamic contours have been held responsible. We report an experiment with Dutch and Chinese listeners which aimed to show that production data and perception data are each other’s opposites for high, low, falling and rising contours. We explain the results, which are consistent with earlier findings, in terms of the compensatory listening strategy of [2], arguing that the perception effects are due to a perceptual compensation of articulatory strategies and
constraints, rather than that differences in production compensate for psycho-acoustic perception effects.

Abstract

Three groups of monolingual listeners, with Standard Chinese, Dutch and Hungarian as their native language, judged pairs of trisyllabic stimuli which differed only in their itch pattern. The segmental structure of the stimuli was made up by the experimenters and presented to subjects as being taken from a little-known language spoken on a South Pacific island. Pitch patterns consisted of a single rise-fall located on or near the second syllable. By and large, listeners selected the stimulus with the higher peak, the later eak, and the higher end rise as the one that signalled a question, regardless of language group. The result is argued to reflect innate, non-linguistic knowledge of the meaning of pitch variation, notably Ohala’s Frequency Code. A significant difference between groups is explained as due to the influence of the mother tongue.

Abstract

This chapter sketches in very general terms the cognitive architecture of both language comprehension and production, as well as the neurobiological infrastructure that makes the human brain ready for language. Focus is on spoken language, since that compares most directly to processing music. It is worth bearing in mind that humans can also interface with language as a cognitive system using sign and text (visual) as well as Braille (tactile); that is to say, the system can connect with input/output processes in any sensory modality. Language processing consists of a complex and nested set of subroutines to get from sound to meaning (in comprehension) or meaning to sound (in production), with remarkable speed and accuracy. The fi rst section outlines a selection of the major constituent operations, from fractionating the input into manageable units to combining and unifying information in the construction of meaning. The next section addresses the neurobiological infrastructure hypothesized to form the basis for language processing. Principal insights are summarized by building on the notion of “brain networks” for speech–sound processing, syntactic processing, and the construction of meaning, bearing in mind that such a neat three-way subdivision overlooks important overlap and shared mechanisms in the neural architecture subserving language processing. Finally, in keeping with the spirit of the volume, some possible relations are highlighted between language and music that arise from the infrastructure developed here. Our characterization of language and its neurobiological foundations is necessarily selective and brief. Our aim is to identify for the reader critical questions that require an answer to have a plausible cognitive neuroscience of language processing.

Abstract

This paper investigates the time and space complexity of word order computation in the psycholinguistically motivated grammar formalism of Performance Grammar (PG). In PG, the first stage of syntax assembly yields an unordered tree ('mobile') consisting of a hierarchy of lexical frames (lexically anchored elementary trees). Associated with each lexica l frame is a linearizer—a Finite-State Automaton that locally computes the left-to-right order of the branches of the frame. Linearization takes place after the promotion component may have raised certain constituents (e.g. Wh- or focused phrases) into the domain of lexical frames higher up in the syntactic mobile. We show that the worst-case time and space complexity of analyzing input strings of length n is O(n5) and O(n4), respectively. This result compares favorably with the time complexity of word-order computations in Tree Adjoining Grammar (TAG). A comparison with Head-Driven Phrase Structure Grammar (HPSG) reveals that PG yields a more declarative linearization method, provided that the FSA is rewritten as an equivalent regular expression.

Abstract

This chapter contains sections titled: Introduction Questions Questioning and the Epistemic Gradient Presuppositions, Agenda Setting and Preferences Social Actions Implemented by Questions Questions as Building Blocks of Institutional Activities Future Directions

Abstract

In human face-to-face communication, language comprehension is a multi-modal, situated activity. However, little is known about how we combine information from these different modalities, and how perceived communicative intentions, often signaled through visual signals, such as eye
gaze, may influence this processing. We address this question by simulating a triadic communication context in which a
speaker alternated her gaze between two different recipients. Participants thus viewed speech-only or speech+gesture
object-related utterances when being addressed (direct gaze) or unaddressed (averted gaze). Two object images followed
each message and participants’ task was to choose the object that matched the message. Unaddressed recipients responded significantly slower than addressees for speech-only
utterances. However, perceiving the same speech accompanied by gestures sped them up to a level identical to
that of addressees. That is, when speech processing suffers due to not being addressed, gesture processing remains intact and enhances the comprehension of a speaker’s message

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

The aim of this paper is to discuss an inherent difficulty of PET (and fMRI) research in language production. On the one hand, language production presupposes some degree of freedom for the subject, on the other hand, interpretability of results presupposes restrictions of this freedom. This difficulty is reflected in the existing PET literature in some neglect of the general principle to design experiments in such a way that the results do not allow for alternative interpretations. It is argued that by narrowing down the scope of experiments a gain in interpretability can be achieved.

Abstract

This chapter reviews the findings of 58 word production experiments using different tasks and neuroimaging techniques. The reported cerebral activation sites are coded in a common anatomic reference system. Based on a functional model of language production, the different word production tasks are analyzed in terms of their processing components. This approach allows a distinction between the core process of word production and preceding task-specific processes (lead-in processes) such as visual or auditory stimulus recognition. The core process of word production is subserved by a left-lateralized perisylvian/thalamic language production network. Within this network there seems to be functional specialization for the processing stages of word production. In addition, this chapter includes a discussion of the available evidence on syntactic production, self-monitoring, and the time course of word production.

Abstract

Models of cognitive processes often include simplifications, idealisations, and fictionalisations, so how should we learn about cognitive processes from such models? Particularly in cognitive science, when many features of the target system are unknown, it is not always clear which simplifications, idealisations, and so on, are appropriate for a research question, and which are highly misleading. Here we use a case-study from studies of language evolution, and ideas from philosophy of science, to illustrate a robustness approach to learning from models. Robust properties are those that arise across a range of models, simulations and experiments, and can be used to identify key causal structures in the models, and the phenomenon, under investigation. For example, in studies of language evolution, the emergence of compositional structure is a robust property across models, simulations and experiments of cultural transmission, but only under pressures for learnability and expressivity. This arguably illustrates the principles underlying real cases of language evolution. We provide an outline of the robustness approach, including its limitations, and suggest that this methodology can be productively used throughout cognitive science. Perhaps of most importance, it suggests that different modelling frameworks should be used as tools to identify the abstract properties of a system, rather than being definitive expressions of theories.

Abstract

n this study we investigated the durational correlates of lexical stress and pitch accent at normal and fast speech rate in Dutch. Previous literature on English shows that durations of lexically unstressed vowels are reduced more than stressed vowels when speakers increase their speech rate. We found that the same holds for Dutch, irrespective of whether the unstressed vowel is schwa or a "full" vowel. In the same line, we expected that vowels in words without a pitch accent would be shortened relatively more than vowels in words with a pitch accent. This was not the case: if anything, the accented vowels were shortened relatively more than the unaccented vowels. We conclude that duration is an important cue for lexical stress, but not for pitch accent.

Abstract

Studies on fast speech have shown that word-level timing of fast speech differs from that of normal rate speech in that unstressed syllables are shortened more than stressed syllables as speech rate increases. An earlier experiment showed that the intelligibility of time-compressed speech could not be improved by making its temporal organisation closer to natural fast speech. To test the hypothesis that segmental intelligibility is more important than prosodic timing in listening to timecompressed speech, the intelligibility of bisyllabic words was tested in three time-compression conditions: either stressed and unstressed syllable were compressed to the same degree, or the stressed syllable was compressed more than the unstressed syllable, or the reverse. As was found before, imitating wordlevel timing of fast speech did not improve intelligibility over linear compression. However, the results did not confirm the hypothesis either: there was no difference in intelligibility between the three compression conditions. We conclude that segmental intelligibility plays an important role, but further research is necessary to decide between the contributions of prosody and segmental intelligibility to the word-level intelligibility of time-compressed speech.

Abstract

The configuration of a spatial layout has a substantial effect on the acquisition and the representation of the environment. In four experiments, we investigated navigation difficulties arising at oblique angled intersections. In the first three studies we investigated specific arrow-fork configurations. In dependence on the branch subjects use to enter the intersection different decision latencies and numbers of errors arise. If subjects see the intersection as a fork, it is more difficult to find the correct way as if it is seen as an arrow. In a fourth study we investigated different heuristics people use while making a detour around a barrier. Detour behaviour varies with the perspective. If subjects learn and navigate through the maze in a field perspective they use a heuristic of preferring right angled paths. If they have a view from above and acquire their knowledge in an observer perspective they use oblique angled paths more often.

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