RGD Reference Report - Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. - Rat Genome Database

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Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development.

Authors: Colognato, H  Ramachandrappa, S  Olsen, IM  Ffrench-Constant, C 
Citation: Colognato H, etal., J Cell Biol. 2004 Oct 25;167(2):365-75.
RGD ID: 2303714
Pubmed: PMID:15504915   (View Abstract at PubMed)
PMCID: PMC2172535   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200404076   (Journal Full-text)

Specific integrins expressed on oligodendrocytes, the myelin-forming cells of the central nervous system, promote either differentiation and survival or proliferation by amplification of growth factor signaling. Here, we report that the Src family kinases (SFKs) Fyn and Lyn regulate each of these distinct integrin-driven behaviors. Fyn associates with alpha6beta1 and is required to amplify platelet-derived growth factor survival signaling, to promote myelin membrane formation, and to switch neuregulin signaling from a phosphatidylinositol 3-kinase to a mitogen-activated protein kinase pathway (thereby changing the response from proliferation to differentiation). However, earlier in the lineage Lyn, not Fyn, is required to drive alphaVbeta3-dependent progenitor proliferation. The two SFKs respond to integrin ligation by different mechanisms: Lyn, by increased autophosphorylation of a catalytic tyrosine; and Fyn, by reduced Csk phosphorylation of the inhibitory COOH-terminal tyrosine. These findings illustrate how different SFKs can act as effectors for specific cell responses during development within a single cell lineage, and, furthermore, provide a molecular mechanism to explain similar region-specific hypomyelination in laminin- and Fyn-deficient mice.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
integrin binding  IDA 2303714RGD: 1310613 and RGD: 628868RGD 
platelet-derived growth factor receptor binding  IPIPdgfra (Rattus norvegicus)2303714 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Csk  (C-terminal Src kinase)
Lyn  (LYN proto-oncogene, Src family tyrosine kinase)


Additional Information