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

Colognato, Holly, Ramachandrappa, Shwetha, Olsen, Inger M. and Ffrench-Constant, Charles ORCID: https://orcid.org/0000-0002-5621-3377 (2004) Integrins direct Src family kinases to regulate distinct phases of oligodendrocyte development. Journal of Cell Biology, 167 (2). pp. 365-375. ISSN 0021-9525

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Abstract

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 α6β1 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 αVβ3- 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.

Item Type: Article
Uncontrolled Keywords: cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 11:31
Last Modified: 13 Aug 2022 02:21
URI: https://ueaeprints.uea.ac.uk/id/eprint/86335
DOI: 10.1083/jcb.200404076

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