Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1995 Nov 17;270(46):27871-5.

Thrombin stimulates phosphorylation of insulin-like growth factor-1 receptor, insulin receptor substrate-1, and phospholipase C-gamma 1 in rat aortic smooth muscle cells.

Author information

  • 1Division of Cardiology, University of Texas Medical Branch, Galveston 77555, USA.

Abstract

It has recently been reported that protein-tyrosine kinase activity is required for thrombin-induced growth in vascular smooth muscle cells (VSMC). In the present study, we have identified several phosphoproteins that are tyrosine-phosphorylated in response to thrombin in quiescent VSMC. These proteins are insulin-like growth factor-1 receptor beta-subunit (IGF-IR beta), insulin receptor substrate-1 (IRS-1), and phospholipase C-gamma 1 (PLC-gamma 1). Thrombin-stimulated phosphorylation of these proteins was rapid; it was maximal at 1 min and reduced thereafter. Thrombin also activated mitogen-activated protein kinases (MAPK) in quiescent VSMC in a biphasic manner with a rapid and larger peak at 10 min (6-fold) followed by a sustained smaller second peak at 2 h (2-fold). Inhibition of protein-tyrosine kinase activity by the use of two structurally different protein-tyrosine kinase inhibitors, genistein and herbimycin A, significantly blocked the thrombin-induced tyrosine phosphorylation of IGF-1R beta, IRS-1, and PLC-gamma 1 and decreased thrombin-stimulated DNA synthesis. In contrast, however, inhibition of protein-tyrosine kinase activity had no effect on thrombin activation of MAPK. Collectively, these findings suggest a role for tyrosine phosphorylation of IGF-IR beta, IRS-1, and PLC-gamma 1 in thrombin-induced mitogenic signaling events in VSMC. Furthermore, while protein tyrosine phosphorylation is essential for thrombin-induced DNA synthesis, it is not required for thrombin-stimulated MAPK activation. Since thrombin rapidly activated Src in VSMC, Src may be involved in the cross-talk between the G-protein-coupled receptor agonist and a tyrosine kinase receptor such as IGF-1R.

PMID:
7499260
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk