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(Received for publication, April 8, 1996, and in revised form, July 15, 1996)
From the Department of Biochemistry and Biophysics and the
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.
Volume 271, Number 46,
Issue of November 15, 1996
pp. 29049-29059
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
and
Department of Pharmacology, University of North Carolina
School of Medicine, Chapel Hill, North Carolina 27599 and the
Department of Neurological Surgery, School of Medicine,
University of Utah, Salt Lake City, Utah 84132
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