title: Revisiting the ERK/Src cortactin switch.
abstract: The filamentous (F)-actin regulatory protein cortactin plays an important role in tumor cell movement and invasion by promoting and stabilizing actin related protein (Arp)2/3-mediated actin networks necessary for plasma membrane protrusion. Cortactin is a substrate for ERK1/2 and Src family kinases, with previous in vitro findings demonstrating ERK1/2 phosphorylation of cortactin as a positive and Src phosphorylation as a negative regulatory event in promoting Arp2/3 activation through neuronal Wiskott Aldrich Syndrome protein (N-WASp). Evidence for this regulatory cortactin "switch" in cells has been hampered due to the lack of phosphorylation-specific antibodies that recognize ERK1/2-phosphorylated cortactin. Our findings with phosphorylation-specific antibodies against these ERK1/2 sites (pS405 and pS418) indicate that cortactin can be co-phosphorylated at 405/418 and tyrosine residues targeted by Src family tyrosine kinases. These results indicate that the ERK/Src cortactin switch is not the sole mechanism by which ERK1/2 and tyrosine phosphorylation events regulate cortactin function in cell systems.
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: 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