Functional interaction between c-Abl and the p21-activated protein kinase γ-PAK

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dc.creatorRoig, Joan
dc.creatorTuazon, Polygena T.
dc.creatorZipfel, Patricia A.
dc.creatorPendergast, Ann Marie
dc.creatorTraugh, Jolinda A.
dc.date2000-12-19
dc.date.accessioned2026-08-02T19:55:45Z
dc.descriptionA member of the p21-activated protein kinase (PAK) family, γ-PAK has cytostatic properties and is activated by cellular stresses such as hyperosmolarity or DNA damage. We report herein that γ-PAK is associated in vivo with the nonreceptor protein tyrosine kinase c-Abl. γ-PAK phosphorylates c-Abl on sites located in the kinase domain, in a region that is implicated in protein–protein interactions and in subcellular localization. Activation of γ-PAK in human embryonic kidney 293T cells by cotransfection with constitutively active Cdc42 induces activation of c-Abl, resulting in increased phosphotyrosine levels. Cotransfection of c-Abl and γ-PAK elicits phosphorylation of γ-PAK on tyrosine and down-regulation of γ-PAK activity, promoting accumulation of inactive γ-PAK. γ-PAK is also phosphorylated in vitro by c-Abl. γ-PAK activity is regulated by ubiquitination and proteolysis in vivo, as shown by immunoblotting with an anti-ubiquitin antibody in the presence of proteasome inhibitors. In summary, we describe a functional interaction between γ-PAK and c-Abl in which γ-PAK stimulates c-Abl tyrosine kinase activity and c-Abl phosphorylates and down-regulates γ-PAK, suggesting the existence of a negative feedback loop between c-Abl and γ-PAK.
dc.identifierhttps://pmc.ncbi.nlm.nih.gov/articles/PMC18921/
dc.identifierhttps://pubmed.ncbi.nlm.nih.gov/11121037/
dc.identifierhttps://doi.org/10.1073/pnas.97.26.14346
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/80025
dc.languageen
dc.publisherNational Academy of Sciences
dc.rightsCopyright © 2000, The National Academy of Sciences
dc.sourceProc Natl Acad Sci U S A
dc.subjectBiological Sciences
dc.titleFunctional interaction between c-Abl and the p21-activated protein kinase γ-PAK
dc.typeText

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