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

Goncharova, E.A.; Vorotnikov, A.V.; Gracheva, E.O.; Wang, C.L.; Panettieri, R.A.; Stepanova, V.V.; Tkachuk, V.A.

Авторы: Goncharova E.A., Vorotnikov A.V., Gracheva E.O., Wang C.L.A, Panettieri R.A., Stepanova V.V., Tkachuk V.A.
Журнал: Biological Chemistry
Том: 383
Номер: 1
Год издания: 2002
Издательство: Walter de Gruyter GmbH & Co. KG
Местоположение издательства: Germany
Первая страница: 115
Последняя страница: 126
DOI: 10.1515/BC.2002.012
Аннотация: 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.
Добавил в систему: Ткачук Всеволод Арсеньевич

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

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