Overexpression of C-terminal Src kinase homologous kinase suppresses activation of Lyn tyrosine kinase required for VLA5-mediated Dami cell spreading.

The Journal of Biological Chemistry
A HiraoNaoto Yamaguchi

Abstract

The Csk homologous kinase (Chk), which is co-expressed with C-terminal Src kinase (Csk) in hematopoietic cells, negatively regulates Src family kinases in vitro with selectivity toward Lyn but not c-Src in platelets. To explore the role of Src family kinases in hematopoietic cell adhesion, we overexpressed Chk in the megakaryocytic cell line Dami and established clones exhibiting a 10-fold increase in the amount of Chk. Overexpression of Chk was found to suppress VLA5 integrin-mediated cell spreading, but not cell attachment, throughout fibronectin (FN) stimulation. Deletion and point mutagenesis analyses of Chk showed that this suppression was dependent upon both the SH3 domain, which is responsible for membrane anchoring, and kinase activity. FN-induced cell spreading accompanied a sustained increase in Lyn activity with coincidental kinetics and the activation of Lyn was also suppressed by overexpression of Chk but not a Chk mutant lacking the SH3 domain. Expression of a truncated Lyn mutant lacking the kinase domain inhibited both cell spreading and Lyn activation upon stimulation with FN. These results suggest that sustained activation of Lyn, which is regulated by membrane-anchored Chk, plays a crucial role in VLA5-mediat...Continue Reading

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Citations

Sep 27, 2008·Experimental Cell Research·Kikuko IkedaNaoto Yamaguchi
May 7, 2008·Experimental Cell Research·Takahisa KugaNaoto Yamaguchi
Mar 8, 2005·Experimental Cell Research·Yuji Nakayama, Naoto Yamaguchi
Oct 4, 2005·Biochimica Et Biophysica Acta·Yuh-Ping ChongHeung-Chin Cheng
Jul 11, 2001·The Journal of Biological Chemistry·C BougeretH Avraham
Dec 26, 2006·The Journal of Biological Chemistry·Kousuke KasaharaNaoto Yamaguchi
Feb 27, 2004·The Journal of Biological Chemistry·Yuh-Ping ChongHeung-Chin Cheng
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shalini Pereira, Clifford Lowell
Jun 12, 1999·Biochemical and Biophysical Research Communications·D J PriceH Avraham
Mar 19, 1999·Biochemical and Biophysical Research Communications·S GrgurevichD W McVicar
Aug 19, 2007·Archives of Biochemistry and Biophysics·Takahisa KugaNaoto Yamaguchi

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