Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-4-3
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1431-6730
pubmed:author
pubmed:issnType
Print
pubmed:volume
383
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
115-26
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration.
pubmed:affiliation
Laboratory of Cell Motility, Institute of Experimental Cardiology, Russian Cardiology Research Center, Moscow.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't