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Volume 271, Number 46, Issue of November 15, 1996 pp. 29049-29059
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

rek, a Gene Expressed in Retina and Brain, Encodes a Receptor Tyrosine Kinase of the Axl/Tyro3 Family

(Received for publication, April 8, 1996, and in revised form, July 15, 1996)

Jacqueline S. Biscardi , Fabienne Denhez , Georg F. Buehler , David A. Chesnutt , Steven C. Baragona , John P. O'Bryan Dagger , Channing J. Der Dagger , James J. Fiordalisi , Daniel W. Fults par and Patricia F. Maness

From the Department of Biochemistry and Biophysics and the Dagger  Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 and the par  Department of Neurological Surgery, School of Medicine, University of Utah, Salt Lake City, Utah 84132

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 chick embryonic brain cDNA library with a DNA probe obtained by reverse transcriptase-polymerase chain reaction of mRNA from Müller glia-like cells 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 fibronectin type III domains with eight predicted N-glycosylation sites. Two consensus src homology 2 domain binding sites are present in the cytoplasmic domain, suggesting that Rek activates several signal transduction pathways. Northern analysis of rek mRNA revealed a 5.5-kilobase transcript in chick brain, retina, and kidney and in primary cultures of retinal Müller glia-like cells. Rek protein was identified by immunoprecipitation and immunoblotting as a 140-kDa protein expressed in the chick retina at embryonic days 6-13, which corresponded to the major period 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 assays. 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 potential when overexpressed, but its normal function is likely to be related to cell-cell recognition events governing the differentiation or proliferation of neural cells.


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