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 cell development, we have cloned a new member of the Eph-family of receptor tyrosine kinases (Mep, for murine eph-family protein). At the amino acid level Mep is 60% identical to the chicken embryonic 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 is followed by a kinase domain. Surprisingly, this kinase domain carries amino acid substitutions in the highly conserved consensus motifs found in all protein tyrosine kinases and known to be crucial for kinase activity. We demonstrate that a bacterial fusion protein of the Mep kinase domain does not have protein tyrosine kinase activity. Analysis of Mep mRNA levels in a variety of mouse tissues shows that Mep is highly expressed in thymus and brain. We have also isolated two additional Mep cDNA clones from thymocytes which are predicted to encode secreted forms of the Mep extracellular domain; mRNAs encoding these secreted isoforms are also expressed in mouse brain.