Linked Life Data

20940300

Source:http://linkedlifedata.com/resource/pubmed/id/20940300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
51
pubmed:dateCreated
2010-12-14
pubmed:abstractText
Integrin ?1?1 is a collagen receptor that down-regulates collagen and reactive oxygen species (ROS) production, and mice lacking this receptor show increased ROS levels and exacerbated glomerular sclerosis following injury. Caveolin-1 (Cav-1) is a multifunctional protein that is tyrosine-phosphorylated in response to injury and has been implicated in ROS-mediated injury. Cav-1 interacts with integrins, and integrin ?1?1 binds/activates T cell protein-tyrosine phosphatase (TCPTP), which is homologous to the tyrosine phosphatase PTP1B known to dephosphorylate Cav-1. In this study, we analyzed whether phosphorylated Cav-1 (pCav-1) is a substrate of TCPTP and if integrin ?1?1 is essential for promoting TCPTP-mediated Cav-1 dephosphorylation. We found that Cav-1 phosphorylation is significantly higher in cells lacking integrin ?1?1 at base line and following oxidative stress. Overexpression of TCPTP leads to reduced pCav-1 levels only in cells expressing integrin ?1?1. Using solid phase binding assays, we demonstrated that 1) purified Cav-1 directly interacts with TCPTP and the integrin ?1 subunit, 2) pCav-1 is a substrate of TCPTP, and 3) TCPTP-mediated Cav-1 dephosphorylation is highly increased by the addition of purified integrin ?1?1 or an integrin ?1 cytoplasmic peptide to which TCPTP has been shown to bind. Thus, our results demonstrate that pCav-1 is a new substrate of TCPTP and that integrin ?1?1 acts as a negative regulator of Cav-1 phosphorylation by activating TCPTP. This could explain the protective function of integrin ?1?1 in oxidative stress-mediated damage and why integrin ?1-null mice are more susceptible to fibrosis following injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40114-24
pubmed:meshHeading
pubmed-meshheading:20940300-Animals, pubmed-meshheading:20940300-CHO Cells, pubmed-meshheading:20940300-Caveolin 1, pubmed-meshheading:20940300-Collagen, pubmed-meshheading:20940300-Cricetinae, pubmed-meshheading:20940300-Cricetulus, pubmed-meshheading:20940300-Enzyme Activation, pubmed-meshheading:20940300-Fibrosis, pubmed-meshheading:20940300-HEK293 Cells, pubmed-meshheading:20940300-Humans, pubmed-meshheading:20940300-Integrin alpha1beta1, pubmed-meshheading:20940300-Mice, pubmed-meshheading:20940300-Mice, Mutant Strains, pubmed-meshheading:20940300-Oxidative Stress, pubmed-meshheading:20940300-Phosphorylation, pubmed-meshheading:20940300-Protein Tyrosine Phosphatase, Non-Receptor Type 2, pubmed-meshheading:20940300-Reactive Oxygen Species, pubmed-meshheading:20940300-Recombinant Proteins
pubmed:year
2010
pubmed:articleTitle
Integrin {alpha}1{beta}1 promotes caveolin-1 dephosphorylation by activating T cell protein-tyrosine phosphatase.
pubmed:affiliation
Department of Medicine, Division of Nephrology, Vanderbilt University, Nashville, Tennessee 37212-2372, USA. corina.borza@vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural