Biochimica et Biophysica Acta, 1072 (1991) 1 !5-127 © 1991 Elsevier Science Publishers B.V. All rights reserved 0304-419X/91/$03.50 115 BBACAN 87237 The Irk family of tyrosine protein kinase receptors Mariano Barbacid, Fabienne Lamballe, Diego Pulido and Riidiger Klein Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ (U.S.A.) (Received 17 December 1990) Contents !. Ir~t,'oduction ............................................................... 115 II. The Irk proto-oncogene ..................................................... 116 !!!. Irk oncogenes ........................................................... 117 A. Molecular structure ...................................................... 117 B. Mechanism of activation .................................................. 1 !8 IV. trk-related genes ......................................................... 120 A. Drosophila Dtrk gene .................................................... 120 B. Mammalian trkB and trkC genes ............................................ 121 V. Chromosomal mapping ..................................................... 122 VI. Expression of the trk gene family in neural tissues .................................. 123 A. Dtrk expression during Drosophila development ................................. 123 B. trk proto-oncogene expression in mouse neural tissues ............................. 124 C. trkB expression in the murine embryonic and adul! nervous system .................... 124 VII. Biological role of the Irk gene family ............................................ 125 Acknowledgements ............................................................ 125 Note added in proof ............................................................. 126 References .................................................................. 126 I. Introduction Since the discovery of tyrosine protein kinases over a decade ago, this gene superfamily has been steadily growing to reach its current size of almost 50 members [1]. A significant fraction of these genes code for cell surface glycoproteins that function as growth factor receptors [2,3]. They include the receptors for insulin, IGF-1, EGF, PDGF A and B, M-CSF, the product of the steel gene and the members of the FGF family. Structuraly related tyrosine kinase genes such as eck, Abbreviations: CNS, central nervous system; PNS, peripheral ner- vous system; NGF, nerve growth factor. Correspondence: M. Barbacid, Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543-4000, U.S.A. eph, ret, ros, sea, etc., are also thought to code for cell surface receptors, although their putative cognate lig- ands remain to be identified [1-3]. The members of the trk gene family, trk [4,5], trk B [6-8], the recently isolated trkC [9] and Drosophila Dtrk (unpublished observations) genes belong to the latter group of tyro- sine kinases. It could be argued that without knowing their ligand(s) and considering our limited kaowledge of intraceilular signal transduction pathways, informa- tion derived from studying these genes has limited physiological relevance. In spite of these limitations, studies involving the trk gene family have already provided valuable information. For instance, the spe- cific pattern of expression of some members of the trk gene family has suggested the presence of distinct sets of neurons in sensory structures of the peripheral ner- vous .;ystem. Moreover, structural studies have re- vealed for the first time, that tyrosine kinase receptor