title: Further insights into cortactin conformational regulation.
abstract: The actin regulatory protein cortactin is involved in multiple signaling pathways impinging on the cortical actin cytoskeleton. Cortactin is phosphorylated by ERK1/2 and Src family tyrosine kinases, resulting in neuronal Wiskott Aldrich Syndrome protein (N-WASp) activation and enhanced actin related protein (Arp)2/3-mediated actin nucleation. Cortactin migrates as an 80/85 kDa doublet when analyzed by SDS-PAGE. Phosphorylation by ERK1/2 is associated with conversion of the 80 kDa to the 85 kDa form, postulated to occur by inducing a conformational alteration that releases the carboxyl-terminal SH3 domain from autoinhibition. Our recent analysis of the 80-85 kDa cortactin "shift" in tumor cells indicates that while ERK1/2 phosphorylation is associated with the 85 kDa shift, this phosphorylation event is not required for the shift to occur, nor does ERK1/2 phosphorylation appreciably alter global cortactin confirmation. These data indicate that additional factors besides ERK1/2 phosphorylation contribute to generating and/or maintaining the activated 85 kDa cortactin form in stimulated cells.
authors.affiliation: Department of Neurobiology and Anatomy; Program in Cancer Cell Biology; Mary Babb Randolph Cancer Center; West Virginia University; Morgantown, WV USA.
authors.forename: Jason V
authors.initials: JV
authors.lastname: Evans
authors.forename: Laura C
authors.initials: LC
authors.lastname: Kelley
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hayes
authors.forename: Amanda Gatesman
authors.initials: AG
authors.lastname: Ammer
authors.forename: Karen H
authors.initials: KH
authors.lastname: Martin
authors.forename: Scott A
authors.initials: SA
authors.lastname: Weed