EHK-1 AND EHK-2 - 2 NOVEL MEMBERS OF THE EPH RECEPTOR-LIKE TYROSINE KINASE FAMILY WITH DISTINCTIVE STRUCTURES AND NEURONAL EXPRESSION

We have identified two novel members of the Eph RTK family, termed Ehk (eph homology kinase) -1 and -2. Compared to the amino acid sequences of various Eph family members, Ehk-1 and Ehk-2 are closest to the Sek and Cek-4/Mek-4/Hek kinases, and both are more similar to the Elk kin ase than they are to the Eck or Eph kinases. Analysis of Ehk-1 cDNAs f rom various brain libraries reveals alternatively spliced transcripts: that can encode five different forms of Ehk-1 transmembrane proteins. By contrast, Ehk-2 cDNAs revealed only a single form of protein codin g region. However, the structure of Ehk-2 differs from all known membe rs of the Eph family based on a 42 amino acid insert positioned betwee n homology regions IV and V in the kinase domain. Ehk-1 and Ehk-2 are almost exclusively expressed in the nervous system. RNA in situ hybrid ization analyses on adult brain show that the Ehks are predominantly e xpressed in neurons and display overlapping, but distinct patterns of expression in various neuronal populations.