title: Phosphorylation of serine 709 in GIT1 regulates protrusive activity in cells.
abstract: G protein-coupled receptor kinase-interacting protein (GIT)1 is a multidomain, adaptor protein that regulates cellular processes, such as migration and protrusive activity, by bringing together various signaling molecules, including PIX, PAK, and paxillin. Mutants of GIT1, which lack the C-terminal paxillin binding domain, fail to mediate its effects on migration and protrusions, suggesting that sites within this domain are critical to GIT1 function. In this study, we show that serine 709, which is located within the paxillin binding domain, regulates GIT1 function. Phosphorylation of serine 709 is necessary for GIT1-induced effects on protrusions. Phosphorylation of this site also regulates GIT1 interaction with paxillin, which could serve to target GIT1 to the leading edge of cells. As shown by an in vitro kinase assay, PAK phosphorylates GIT1 on serine 709. Taken together, our results indicate that GIT1 phosphorylation on serine 709 increases its binding to paxillin and regulates protrusive activity in cells.
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, VA 22908, USA. donna.webb@vanderbilt.edu
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Webb
authors.forename: Mykola
authors.initials: M
authors.lastname: Kovalenko
authors.forename: Leanna
authors.initials: L
authors.lastname: Whitmore
authors.forename: Alan F
authors.initials: AF
authors.lastname: Horwitz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D022081:Cell Surface Extensions / Q000502:physiology*; D006224:Cricetinae; D006801:Humans; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D054462:p21-Activated Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C485647:GIT1 protein, human; D051419:Paxillin; D012694:Serine; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases