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PKC phosphorylation increases the ability of AFAP-110 to cross-link action filaments.
Qian-Y; Baisden-JM; Cherezova-L; Summy-JM; Guappone-Koay-A; Shi-X; Mast-T; Pustula-J; Zot-HG; Mazloum-N; Lee-MY; Flynn-DC
Mol Biol Cell 2002 Jul; 13(7):2311-2322
The actin filament-associated protein and Src-binding partner, AFAP-110, is an adaptor protein that links signaling molecules to actin filaments. AFAP-110 binds actin filaments directly and multimerizes through a leucine zipper motif. Cellular signals downstream of Src(527F) can regulate multimerization. Here, we determined recombinant AFAP-110 (rAFAP-110)-bound actin filaments cooperatively, through a lateral association. We demonstrate rAFAP-110 has the capability to cross-link actin filaments, and this ability is dependent on the integrity of the carboxy terminal actin binding domain. Deletion of the leucine zipper motif or PKC phosphorylation affected AFAP-110's conformation, which correlated with changes in multimerization and increased the capability of rAFAP-110 to cross-link actin filaments. AFAP-110 is both a substrate and binding partner of PKC. On PKC activation, stress filament organization is lost, motility structures form, and AFAP-110 colocalizes strongly with motility structures. Expression of a deletion mutant of AFAP-110 that is unable to bind PKC blocked the effect of PMA on actin filaments. We hypothesize that upon PKC activation, AFAP-110 can be cooperatively recruited to newly forming actin filaments, like those that exist in cell motility structures, and that PKC phosphorylation effects a conformational change that may enable AFAP-110 to promote actin filament cross-linking at the cell membrane.
Proteins; In-vitro-study; Cellular-reactions; Cellular-structures; Genes
Daniel C. Flynn, The Mary Babb Randolph Cancer Center and the Department of Microbiology and Immunology, West Virginia University, Morgantown, WV 26506-9300
Issue of Publication
Disease and Injury: Hearing Loss
Molecular Biology of the Cell
WV; MI; NY
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