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Biol Chem. 2002 Jan;383(1):115-26.

Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration.

Author information

1
Laboratory of Cell Motility, Institute of Experimental Cardiology, Russian Cardiology Research Center, Moscow.

Abstract

We have explored intracellular pathways involved in the urokinase type plasminogen activator (urokinase or uPA)-stimulated migration of human airway smooth muscle cells (hAWSMC). Using a set of uPA mutants we found that protease activity, growth factor-like and kringle domains of uPA differentially contribute to activation of p42/p44erk1,2 and p38 MAP-kinases. Consistent with our earlier data [Mukhina et al., J. Biol. Chem. 275 (2000), 16450-16458], the kringle domain of uPA was sufficient and required to stimulate cell motility. Here we report that uPA mutants containing the kringle domain specifically activate the p38 MAP-kinase pathway and actomyosin by increasing phosphorylation of the critical Ser-19 on the myosin regulatory light chain and MAP-kinase sites of the actin-associated regulatory protein caldesmon. While pharmacological inhibition of p38 MAP-kinase activation did not affect myosin light chain phosphorylation, it blocked the increase in caldesmon phosphorylation and uPA-stimulated migration of hAWSMC on a collagen-coated surface. We conclude that activation of p38 MAP-kinase and downstream phosphorylation of non-muscle caldesmon is essential for urokinase-stimulated smooth muscle cell migration.

PMID:
11930938
DOI:
10.1515/BC.2002.012
[Indexed for MEDLINE]

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