Regulation of mitogen-activated protein kinase activation by the cytoplasmic domain of the alpha6 integrin subunit
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
1998-04-16Keywords
1-Phosphatidylinositol 3-KinaseAntigens, CD
Calcium-Calmodulin-Dependent Protein Kinases
Cell Movement
Enzyme Activation
Flavonoids
Integrin alpha6
Laminin
Macrophages
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
*Mitogen-Activated Protein Kinases
Protein Kinase C
Ribosomal Protein S6 Kinases
ras Proteins
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
We examined the possibility that the alpha6A and alpha6B cytoplasmic domain variants of the alpha6beta1 integrin differentially activate p42 and p44 mitogen-activated protein (MAP) kinases. P388D1 macrophages that express equivalent surface levels of either the alpha6Abeta1 or alpha6Bbeta1 integrin were used to examine this issue. Adhesion to laminin-1 mediated by the alpha6Abeta1 integrin triggered activation of a substantial fraction of total p42 and p44 MAP kinases as assessed using a mobility shift assay, immunoblot analysis with a phosphospecific MAP kinase antibody, and an immune complex kinase assay. In contrast, ligation of the alpha6Bbeta1 integrin did not trigger significant MAP kinase activation. These data were confirmed by antibody clustering of the alpha6beta1 integrins. Both the alpha6Abeta1 and alpha6Bbeta1 integrins were capable of activating the p70 ribosomal S6 kinase and this activation, unlike MAP kinase activation, is dependent on phosphoinositide 3-OH kinase. Activation of MAP kinase by alpha6beta1 requires both Ras and protein kinase C activity. A functional correlate for differential activation of MAP kinase was provided by the findings that the alpha6Abeta1 transfectants migrated significantly better on laminin than the alpha6Bbeta1 transfectants and this migration was dependent on MAP kinase activity based on the use of the MAP kinase kinase (MEK1) inhibitor PD98059. Our findings demonstrate that the alpha6beta1 integrin can activate MAP kinase, that this activation is regulated by the cytoplasmic domain of the alpha6 subunit, and that it relates to alpha6beta1-mediated migration.Source
J Biol Chem. 1998 Mar 6;273(10):5903-7.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26288PubMed ID
9488728Related Resources
Link to Article in PubMedCollections
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