REK, A GENE EXPRESSED IN RETINA AND BRAIN, ENCODES A RECEPTOR TYROSINE KINASE OF THE AXL TYRO3 FAMILY/

Rek (retina-expressed kinase) has been identified as a putative novel receptor-type tyrosine kinase of the Axl/Tyro3 family with a potential role in neural cell development, rek clones were isolated from a chic k embryonic brain cDNA library with a DNA probe obtained by reverse tr anscriptase-polymerase chain reaction of mRNA from Muller glia-like ce lls cultured from chick embryonic retina. Sequence analysis indicated that Rek is a protein of 873 amino acids with an extracellular region composed of two immunoglobulin-like domains followed by two fibronecti n type III domains with eight predicted N-glycosylation sites. Two con sensus src homology 2 domain binding sites are present in the cytoplas mic domain, suggesting that Rek activates several signal transduction pathways. Northern analysis of rek mRNA revealed a 5.5-kilobase transc ript in chick brain, retina, and kidney and in primary cultures of ret inal Muller glia-like cells. Rek protein was identified by immunopreci pitation and immunoblotting as a 140-kDa protein expressed in the chic k retina at embryonic days 6-13, which corresponded to the major perio d of neuronal and glial differentiation. Transfection of rek cDNA into COS cells resulted in transient expression of a putative precursor of 106 kDa that autophosphorylated in immune complex protein kinase assa ys. Overexpression of rek cDNA in mouse NIH3T3 fibroblasts resulted in activation of the 140-kDa rek kinase and induction of morphologically transformed foci. These properties indicated that Rek has oncogenic p otential when overexpressed, but its normal function is likely to be r elated to cell-cell recognition events governing the differentiation o r proliferation of neural cells.