Co-expression with BCR induces activation of the FES tyrosine kinase and phosphorylation of specific N-terminal BCR tyrosine residues.

The Journal of Biological Chemistry
J Li, T E Smithgall

Abstract

The human BCR gene encodes a protein with serine/threonine kinase activity and regulatory domains for the small G-proteins RAC and CDC42. Previous work in our laboratory has established that BCR is a substrate for c-FES, a non-receptor tyrosine kinase linked to myeloid growth and differentiation. Tyrosine phosphorylation led to the association of BCR with the RAS guanine nucleotide exchange complex GRB2-SOS in vivo via the GRB2 SH2 domain, linking BCR to RAS signaling (Maru, Y., Peters, K. L., Afar, D. E. H., Shibuya, M., Witte, O. N., and Smithgall, T. E. (1995) Mol. Cell. Biol. 15, 835-842). In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Mutagenesis of BCR Tyr-177 to Phe completely abolished FES-induced BCR binding to the GRB2 SH2 domain, identifying Tyr-177 as an additional phosphorylation site for FES. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1. ...Continue Reading

References

May 30, 1991·Nature·D DiekmannA Hall
Oct 24, 1995·Proceedings of the National Academy of Sciences of the United States of America·T H ChuangG M Bokoch
Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·J E LadburyJ Schlessinger
Aug 25, 1995·Cell·A B Vojtek, J A Cooper
Mar 10, 1995·Cell·J W VonckenJ Groffen
Mar 1, 1996·Molecular and Cellular Biology·J LiuR B Arlinghaus

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Citations

May 10, 2001·International Journal of Hematology·Y Maru
Jul 3, 2002·The EMBO Journal·Norihiro MitsuiShigeru Yanagi
Mar 23, 2002·Molecular and Cellular Biology·Ralph A ZirngiblPeter A Greer
Jun 17, 2003·Molecular and Cellular Biology·G RadziwillK Moelling
May 3, 2011·Progress in Neurobiology·Kimberley F ToliasKyongmi Um
Oct 8, 2005·EMBO Reports·Angelika Ress, Karin Moelling
May 29, 2002·Oncogene·Blanca Scheijen, James D Griffin
May 8, 2002·Nature Reviews. Molecular Cell Biology·Peter Greer
Aug 12, 1999·Oncogene·Y WuR B Arlinghaus
Apr 18, 1998·The Journal of Biological Chemistry·K L NelsonT E Smithgall

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