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Title
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Eps8, a substrate for the epidermal growth factor receptor kinase, enhances EGF-dependent mitogenic signals.
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Authors
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F.Fazioli,
L.Minichiello,
V.Matoska,
P.Castagnino,
T.Miki,
W.T.Wong,
P.P.Di Fiore.
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Ref.
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Embo J, 1993,
12,
3799-3808.
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PubMed id
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Abstract
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A method which allows direct cloning of intracellular substrates for receptor
tyrosine kinases (RTKs) was developed. By applying this technique to the study
of the epidermal growth factor receptor (EGFR) signaling pathway, we have
isolated a cDNA, designated eps8, which predicts a approximately 92 kDa protein
containing an SH3 domain. Eps8 also contains a putative nuclear targeting
sequence. Antibodies specific to the eps8 gene product recognize a protein of
M(r) 97 kDa and a minor 68 kDa component, which are closely related, as
demonstrated by V8 proteolytic mapping. The product of the eps8 gene is
tyrosine-phosphorylated in vivo following EGF stimulation of intact cells and
associates with the EGFR, despite the lack of a functional SH2 domain. Several
other RTKs are also able to phosphorylate p97eps8. Thus, the eps8 gene product
represents a novel substrate for RTKs. Adoptive expression of the eps8 cDNA in
fibroblastic or hematopoietic target cells expressing the EGFR resulted in
increased mitogenic response to EGF, implicating the eps8 gene product in the
control of mitogenic signals.
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