Linked Life Data

11739394

Source:http://linkedlifedata.com/resource/pubmed/id/11739394

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-2-18
pubmed:abstractText
Recent studies from our laboratory have shown that insulin stimulates myosin-bound phosphatase (MBP) in vascular smooth muscle cells (VSMCs) by decreasing site-specific phosphorylation of the myosin-bound subunit (MBS) of MBP via nitric oxide/cGMP-mediated Rho/Rho kinase inactivation. Here we tested potential interactions between Rho kinase and insulin signaling pathways. In control VSMCs, insulin inactivates ROK-alpha, the major Rho kinase isoform in VSMCs, and inhibits thrombin-induced increase in ROK-alpha association with the insulin receptor substrate-1 (IRS-1). Hypertension (in spontaneous hypertensive rats) or expression of an active RhoA(V14) up-regulates Rho kinase activity and increases ROK-alpha/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation. In contrast, expression of dominant negative RhoA or cGMP-dependent protein kinase type I alpha inactivates Rho kinase, abolishes ROK-alpha/IRS-1 association, and potentiates insulin-induced tyrosine phosphorylation and PI3-kinase activation leading to decreased MBS(T695) phosphorylation and decreased MBP inhibition. Collectively, these results suggest a novel function for ROK-alpha in insulin signal transduction at the level of IRS-1 and potential cross-talk between cGMP-dependent protein kinase type I alpha, Rho/Rho kinase signaling, and insulin signaling at the level of IRS-1/PI3-kinase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6214-22
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:11739394-Animals, pubmed-meshheading:11739394-Aorta, pubmed-meshheading:11739394-Cells, Cultured, pubmed-meshheading:11739394-Enzyme Activation, pubmed-meshheading:11739394-Hypertension, pubmed-meshheading:11739394-Insulin, pubmed-meshheading:11739394-Insulin Receptor Substrate Proteins, pubmed-meshheading:11739394-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:11739394-Isoenzymes, pubmed-meshheading:11739394-Male, pubmed-meshheading:11739394-Muscle, Smooth, Vascular, pubmed-meshheading:11739394-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11739394-Phosphoproteins, pubmed-meshheading:11739394-Phosphorylation, pubmed-meshheading:11739394-Phosphoserine, pubmed-meshheading:11739394-Protein-Serine-Threonine Kinases, pubmed-meshheading:11739394-Rats, pubmed-meshheading:11739394-Rats, Inbred SHR, pubmed-meshheading:11739394-Rats, Inbred WKY, pubmed-meshheading:11739394-Signal Transduction, pubmed-meshheading:11739394-rho-Associated Kinases
pubmed:year
2002
pubmed:articleTitle
Active Rho kinase (ROK-alpha ) associates with insulin receptor substrate-1 and inhibits insulin signaling in vascular smooth muscle cells.
pubmed:affiliation
Diabetes Research Laboratory, Winthrop University Hospital, Mineola, New York 11501, USA. nbegum@winthrop.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't