CLONING AND MESSENGER-RNA EXPRESSION ANALYSIS OF A NOVEL HUMAN PROTOONCOGENE, C-MER

A human B-lymphoblastoid lambdagt11 expression library was screened us ing anti-phosphotyrosine antibodies yielding complementary DNAs encodi ng active tyrosine kinases. The resulting clones were used to obtain t he sequence of a novel 984 amino acid transmembrane tyrosine kinase. A nalysis of the complementary DNA revealed extracellular immunoglobulin and fibronectin type III domains and the unusual kinase signature seq uence KWIAIES; all are characteristic of the axl family of tyrosine ki nases. The novel tyrosine kinase was not expressed in normal B- and T- lymphocytes but, unlike axl, was expressed in numerous neoplastic B- a nd T-cell lines. Transcripts for the novel receptor-like tyrosine kina se were detected in normal peripheral blood monocytes and bone marrow. One alternatively spliced transcript was detected which contained an insert in the membrane proximal region that could encode for a truncat ed, soluble receptor. Sequence comparison shows that the kinase may be the human protooncogene for the recently isolated chicken retroviral oncogene v-ryk (recently renamed v-eyk), a truncated tyrosine kinase w hose expression by retroviral infection produced sarcomas in chickens. The intracellular domain of the human kinase shows 83% similarity and 71% identity to v-ryk. Since the ryk designation has been used to nam e another tyrosine kinase and an analysis of RNA expression demonstrat ed that this novel human kinase is expressed in monocytes and tissues of epithelial and reproductive origin, we have designated our novel pr otooncogene c-mer.