A NEW MEMBER OF THE EPH FAMILY OF RECEPTORS THAT LACKS PROTEIN-TYROSINE KINASE-ACTIVITY

Using a PCR-based screen to identify tyrosine kinases involved in T ce ll development, we have cloned a new member of the Eph-family of recep tor tyrosine kinases (Mep, for murine eph-family protein). At the amin o acid level Mep is 60% identical to the chicken embyronic kinase Cek9 . Sequence analysis indicates that the predicted extracellular portion of Mep bears an Ig-like domain, a cysteine-rich region, and sequences homologous to fibronectin type III. The transmembrane region of Mep i s followed by a kinase domain. Surprisingly, this kinase domain carrie s amino acid substitutions in the highly conserved consensus motifs fo und in all protein tyrosine kinases and known to be crucial for kinase activity. We demonstrate that a bacterial fusion protein of the Mep k inase domain does not have protein tyrosine kinase activity. Analysis of Mep mRNA levels in a variety of mouse tissues shows that Mep is hig hly expressed in thymus and brain. We have also isolated two additiona l Mep cDNA clones from thymocytes which are predicted to encode secret ed forms of the Mep extracellular domain; mRNAs encoding these secrete d isoforms are also expressed in mouse brain.