IDENTIFICATION OF A COMPLETE CEK7 RECEPTOR PROTEIN-TYROSINE KINASE CODING SEQUENCE AND CDNAS OF ALTERNATIVELY SPLICED TRANSCRIPTS

Receptor protein tyrosine kinases (RPTK) are critical components of si gnal transduction pathways in multicellular organisms. Identification of new RPTK constitutes an initial step in understanding the variety o f signalling pathways in which these proteins participate. In this stu dy, a cDNA containing a complete coding sequence for Cek7 (chicken RPT K) has been cloned from a chicken embryo expression library using anti -phosphotyrosine antibodies (Ab). Cek7 is a member of the EPH (human R PTK) subfamily of RPTK; this subfamily is characterized by extracellul ar domains containing an immunoglobulin-like motif, a Cys-rich region and two fibronectin type-III repeats. Analysis of additional cDNAs rev ealed that two positions of alternative splicing in primary transcript s may produce several isoforms of this RPTK; cDNAs corresponding to th ree isoforms of this receptor are reported. These isoforms are predict ed to have altered extracellular ligand-binding domains and/or altered cytoplasmic juxtamembrane regions. The nucleotide sequence of cek7 cD NAs identified in this study diverges at the 3' end from the sequence found in a recently described partial cek7 cDNA [Sajjadi and Pasquale, Oncogene 8 (1993) 1807-1813]. Therefore, a third position of alternat ive splicing may produce Cek7 RPTK with divergent C-terminal tails. RN A blot analysis revealed expression of this receptor at highest levels in the central nervous system and eyes of 10-day-old chicken embryos.