Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
1997-12-22
pubmed:abstractText
Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes. We and others have suggested that caveolin functions as a scaffolding protein to organize and concentrate certain caveolin-interacting signaling molecules within caveolae membranes. In this regard, it has been shown that a 20-amino acid membrane-proximal region of the cytosolic NH2-terminal domain of caveolin is sufficient to mediate the interaction of caveolin with signaling proteins, namely G-proteins, Src-like kinases, eNOS, and H-Ras. This caveolin-derived protein domain has been termed the caveolin-scaffolding domain. Binding of the caveolin-scaffolding domain functionally suppresses the activity of G-protein alpha subunits, eNOS, and Src-like kinases, suggesting that caveolin binding may also play a negative regulatory role in signal transduction. Here, we report the direct interaction of caveolin with a growth factor receptor, EGF-R, a known caveolae-associated receptor tyrosine kinase. Two consensus caveolin binding motifs have been previously defined using phage display technology. One of these motifs is present within the conserved kinase domains of most known receptor tyrosine kinases (termed region IX). We now show that this caveolin binding motif within the kinase domain of the EGF-R can mediate the interaction of the EGF-R with the scaffolding domains of caveolins 1 and 3 but not with caveolin 2. In addition, the scaffolding domains of caveolins 1 and 3 both functionally inhibit the autophosphorylation of the EGF-R kinase in vitro. Importantly, this caveolin-mediated inhibition of the EGF-R kinase could be prevented by the addition of an EGF-R-derived peptide that (i) contains a well conserved caveolin binding motif and (ii) is located within the kinase domain of the EGF-R and most known receptor tyrosine kinases. Similar results were obtained with protein kinase C, a serine/threonine kinase, suggesting that caveolin may function as a general kinase inhibitor. The implications of our results are discussed within the context of caveolae-mediated signal transduction. In this regard, caveolae-coupled signaling might explain how linear signaling pathways can branch and interconnect extensively, forming a signaling module or network.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30429-38
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9374534-Alanine, pubmed-meshheading:9374534-Amino Acid Sequence, pubmed-meshheading:9374534-Amino Acid Substitution, pubmed-meshheading:9374534-Animals, pubmed-meshheading:9374534-Binding, Competitive, pubmed-meshheading:9374534-Binding Sites, pubmed-meshheading:9374534-CHO Cells, pubmed-meshheading:9374534-Caveolin 1, pubmed-meshheading:9374534-Caveolins, pubmed-meshheading:9374534-Cell Line, pubmed-meshheading:9374534-Cell Membrane, pubmed-meshheading:9374534-Cricetinae, pubmed-meshheading:9374534-Humans, pubmed-meshheading:9374534-Membrane Proteins, pubmed-meshheading:9374534-Molecular Sequence Data, pubmed-meshheading:9374534-Protein-Serine-Threonine Kinases, pubmed-meshheading:9374534-Protein-Tyrosine Kinases, pubmed-meshheading:9374534-Receptor, Epidermal Growth Factor, pubmed-meshheading:9374534-Receptor, Insulin, pubmed-meshheading:9374534-Receptor, erbB-2, pubmed-meshheading:9374534-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:9374534-Signal Transduction, pubmed-meshheading:9374534-Structure-Activity Relationship
pubmed:year
1997
pubmed:articleTitle
Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities.
pubmed:affiliation
The Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't