Linked Life Data

17403031

Source:http://linkedlifedata.com/resource/pubmed/id/17403031

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-5-2
pubmed:abstractText
Both hyaluronan [HA, the major glycosaminoglycans in the extracellular matrix (ECM)] and CD44 (a primary HA receptor) are associated with astrocyte activation and tissue repair following central nervous system (CNS) injury. In this study we investigated the question of whether HA-CD44 interaction influences astrocyte signaling and migration. Our data indicated that HA binding to the cultured astrocytes stimulated Rac1 signaling and cytoskeleton-mediated migration. To determine the cellular and molecular basis of these events, we focused on PKN gamma, a Rac1-activated serine/threonine kinase in astrocytes. We determined that HA binding to astrocytes stimulated Rac1-dependent PKN gamma kinase activity which, in turn, up-regulated the phosphorylation of the cytoskeletal protein, cortactin, and attenuated the ability of cortactin to cross-link F-actin. Further analyses indicated that the N-terminal antiparallel coiled-coil (ACC) domains of PKN gamma interacted with Rac1, and transfection of astrocytes with PKN gamma-ACCcDNA inhibited PKN gamma activity. Over-expression of the PKN gamma-ACC domain also functions as a dominant-negative mutant to block HA/CD44-mediated PKN gamma activation of cortactin and astrocyte migration. Taken together, these findings strongly suggest that hyaluronan/CD44 interaction with Rac1-PKN gamma plays a pivotal role in cytoskeleton activation and astrocyte migration. These newly discovered HA/CD44-induced astrocyte function may provide important insight into novel therapeutic treatments for tissue repair following CNS injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1002-17
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hyaluronan-CD44 interaction stimulates Rac1 signaling and PKN gamma kinase activation leading to cytoskeleton function and cell migration in astrocytes.
pubmed:affiliation
Department of Medicine, University of California San Francisco, Endocrine Unit (111 N), San Francisco VA Medical Center, San Francisco, CA 94121, USA. lilly.bourguignon@ucsf.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural