Vasoconstrictor‐induced protein‐tyrosine phosphorylation in cultured vascular smooth muscle cells

Abstract

In cultured rat aortic smooth muscle cells, angiotensin II induced tyrosine phosphorylation of at least 9 proteins with molecular masses of 190, 117, 105.82,79,77,73,45 and 40 kDa in time-and dose-dependent manners. Other vasoconstrictors such as [Arglvasopressin, 5-hydroxytryptamine and norepinephrine induced the tyrosine phosphorylation of the same set of proteins as angiotensin II. The tyrosine phosphorylation of these proteins was mimicked by the protein kinase C-activating phorbol ester, phorbol 12 myristate 13-acetate, and the CaZ+ ionophorc, ionomycin. These results demonstrate that the vasoconstrictors stimulate the tyrosine phosphorylation of several proteins in vascular smooth muscle cells and suggest that the tyrosine phosphorylation reactions are the events distal to the activation of protein kinase C and Ca2+ mobilization in the intracellular signalling pathways of the vasoconstrictors.

Effects of tyrosine kinase inhibitors on the contractility of rat mesenteric resistance arteries

“…This observation was supported by the similar potency of the tyrphostins against the contraction induced by calcium and by calcium plus GTP and NA in the x-toxin-permeabilized preparation. It may not be surprising that agonist independent contraction (K+-induced contraction of the intact arteries and calcium-induced contraction of the a-toxin permeabilized preparation) was inhibited by TKIs, since it has been shown in cultured vascular smooth muscle cells (Tsuda et al, 1991) that the calcium ionophore, ionomycin, can induce tyrosine phosphorylation. In fact, the tyrosine phosphorylation pattern induced by the ionophore was not dissimilar to that induced by vasoconstrictors including NA (Tsuda et al, 1991).…”

“…(Bishop, 1987;Draetta et al, 1988), cellular interactions with the extracellular matrix (Schaller & Parsons, 1993) to force development (Berk et al, 1986;Yang et al, 1992). Conversely, classical constrictor agonists like angiotensin II, vasopressin and carbachol have been shown to activate smooth muscle tyrosine kinase and cause tyrosine phosphorylation (Tsuda et al, 1991), and have growth promoting effects. Thus, the tyrosine phosphorylation associated with the application of these hormones could be of importance for both the growth response and the contractile response of these cells.…”

Inhibitory effects of genistein on ATP‐sensitive K+ channels in rabbit portal vein smooth muscle

“…Evidence has been accumulating for some years now that tyrosine kinases are involved in receptor-mediated current inhibition, and in contraction and cell-signalling (Williams, 1989;Tsuda. et al, 1991;Wijetunge et al, 1992;Huang et al, 1993;Hollenberg, 1994;Felder, 1995;Wang & Salter, 1994;Moss et al, 1995;Wijetunge & Hughes, 1995;Hatakeyama et al, 1996).…”

Molecular and cellular mechanisms of action of angiotensin II (AT1) receptors in vascular smooth muscle

“…AII induces tyrosine phosphorylation of multiple proteins in cultured rat aortic vascular smooth muscle cells. 89,90 A lesser and more transient degree of tyrosine phosphorylation was seen in human aortic smooth muscle cells. 71 Focal adhesion kinase (p125FAK), 91 paxillin, 92,91 pp60src 93 and MAP kinases 71 (also known as ERK1 and ERK2) have all been identified as important targets in rat smooth muscle cells.…”

“…Inhibition of pp60src by anti-src antibodies inhibits AII-induced activation of PLC-␥, p21 ras and prevents proliferation in permeabilised rat aortic smooth muscle cells. 93 There is also evidence that a Ca 2+ -dependent tyrosine kinase may contribute to AII-induced tyrosine phosphorylation, possibly in conjunction with PKC, 89 since tyrosine phosphorylation of several proteins 97 including paxillin can be blocked by preventing the rise in [Ca 2+ ] i following AII. It has been suggested that this Ca 2+ -dependent tyrosine kinase could be related to another Ca 2+ -dependent tyrosine kinase, PYK2, previously described in neuronal cells.…”