Linked Life Data

11850825

Source:http://linkedlifedata.com/resource/pubmed/id/11850825

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-2-18
pubmed:abstractText
The colony-stimulating factor-1 (CSF-1) receptor is a protein-tyrosine kinase that regulates the proliferation and differentiation of monocyte and macrophage precursors. Binding of CSF-1 to its receptor results in activation of the kinase domain and autophosphorylation on a number of tyrosine residues. Phosphorylated tyrosine residues function as binding sites for SH2 domain-containing signaling proteins. It is known that activated receptors are internalized and degraded, but the mechanics of this process remain largely unknown. Recently, evidence has started to emerge that the ubiquitin-protein ligase c-Cbl is involved in CSF-1 receptor degradation. In addition, there is evidence that the CSF-1 receptor carboxy-terminus is involved in down regulation of the receptor. Here we show that the c-Cbl tyrosine kinase-binding (TKB) domain binds in vitro and in vivo to the CSF-1 receptor. Binding is dependent on the receptor's protein-kinase activity. Deletion of the carboxy-terminus or mutation of Tyr 973 blocks binding. We further provide evidence that the CSF-1 receptor's carboxy-terminus is a substrate for autophosphorylation. Our observations are consistent with a model in which receptor autophosphorylation at Tyr 973 creates a binding site for c-Cbl. Association of c-Cbl with the receptor leads to ubiquitination, followed by receptor degradation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1079-89
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor's carboxy-terminus.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0601, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.