Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells

Kentaro Shimokado, Tasuku Yokota, Kazuo Umezawa, Toshiyuki Sasaguri, Jun Ogata

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


The effects of protein tyrosine kinase inhibitors on platelet-derived growth factor (PDGF)-induced chemotaxis in cultured rat aortic smooth muscle cells (SMCs) were investigated to elucidate the role of tyrosine phosphorylation in the chemotaxis of vascular SMCs. Two tyrosine kinase inhibitors, methyl 2,5-dihydroxycinnamate and genistein, inhibited PDGF-induced chejnotaxis, the IC50 being 5 and 150 μmol/L, respectively. Methyl cinnamate and genistein partly inhibited the adhesion of SMC to collagen-coated dishes. A chemotaxis assay using double-well culture dishes revealed that both agents also inhibited cell migration after adhesion. H-7, a C kinase inhibitor, did not inhibit either chemotaxis or SMC adhesion at 100 μmol/L. Western blot analysis using anti-phosphotyrosine revealed that the tyrosine kinase inhibitors inhibited the tyrosine phosphorylation of at least two proteins of molecular weight 85 and 95 kD under our experimental conditions. An immunocytochemical study revealed that these inhibitors eliminated tyrosine phosphorylation along the cell margins; these agents also inhibited the reorganization of microtubules and stress fibers, both of which are involved in directional cell locomotion. These findings suggest that tyrosine kinases may play an important role in SMC chemotaxis.

Original languageEnglish
Pages (from-to)973-981
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number6
Publication statusPublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Protein tyrosine kinase inhibitors inhibit chemotaxis of vascular smooth muscle cells'. Together they form a unique fingerprint.

Cite this