Linked Life Data

9218495

Source:http://linkedlifedata.com/resource/pubmed/id/9218495

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
29
pubmed:dateCreated
1997-8-18
pubmed:abstractText
The c-fes proto-oncogene encodes a non-receptor tyrosine kinase (Fes) that has been implicated in cytokine receptor signal transduction and myeloid differentiation. Previous work from our laboratory has shown that Fes autophosphorylates via an intermolecular mechanism more commonly associated with growth factor receptor tyrosine kinases. Analysis of the Fes amino acid sequence with the COILS algorithm indicates that the N-terminal region of the protein has a very high probability of forming coiled-coil structures often associated with oligomeric proteins. These findings suggest that oligomerization may be a prerequisite for trans-autophosphorylation and activation of Fes. To establish whether the active form of Fes is oligomeric, we performed gel-filtration experiments with recombinant Fes and found that it eluted as a single symmetrical peak of approximately 500 kDa. No evidence of the monomeric, 93-kDa form of the protein was observed. Deletion of the unique N-terminal domain (amino acids 1-450, including the coiled-coil homology region) completely abolished the formation of oligomers. Furthermore, co-precipitation assays demonstrated that an immobilized glutathione S-transferase fusion protein containing the Fes N-terminal region bound to full-length Fes but not to a mutant lacking the N-terminal region. Similarly, a recombinant Fes N-terminal domain protein was readily cross-linked in vitro, whereas the SH2 and kinase domains were refractory to cross-linking. Incubation of wild-type Fes with a kinase-inactive Fes mutant or with the isolated N-terminal region suppressed Fes autophosphorylation in vitro, suggesting that oligomerization may be essential for autophosphorylation of full-length Fes. The presence of an oligomerization function in the Fes family of tyrosine kinases suggests a novel mechanism for non-receptor protein-tyrosine kinase regulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18498-503
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Oligomerization of the Fes tyrosine kinase. Evidence for a coiled-coil domain in the unique N-terminal region.
pubmed:affiliation
Eppley Institute for Research in Cancer and the Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't