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

Atsushi Hirao, Xu Ling Huang, Toshio Suda, Naoto Yamaguchi

Research output: Contribution to journalArticle

30 Citations (Scopus)

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-mediated cell spreading but not cell attachment to a FN substrate.

Original languageEnglish
Pages (from-to)10004-10010
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number16
DOIs
Publication statusPublished - 1998 Apr 17

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Overexpression of C-terminal Src kinase homologous kinase suppresses activation of Lyn tyrosine kinase required for VLA5-mediated Dami cell spreading'. Together they form a unique fingerprint.

  • Cite this