title: Src-stimulated IRTKS phosphorylation enhances cell migration.
abstract: Insulin receptor tyrosine kinase substrate (IRTKS) has been demonstrated to be a scaffold protein involved in plasma membrane deformation and actin cytoskeleton remodeling. IRTKS is tyrosine phosphorylated in response to insulin stimulation. However, the mechanism and function of IRTKS phosphorylation remains unclear. Here, we report that overexpression of IRTKS increases the speed of wound closure of HT1080 cells in a Src-dependent manner. Active Src phosphorylates IRTKS in vivo and in vitro. Deletion mapping and mutation analysis revealed that six tyrosine residues (Y37, Y156, Y163, Y274, Y293 and Y439) were Src-stimulated phosphorylation sites on IRTKS. Disruption of Src-stimulated IRTKS phosphorylation abolished the effect of IRTKS on wound closure. Collectively, these data suggest Src-stimulated IRTKS phosphorylation is essential for its function in cell motility.
authors.affiliation: School of Biotechnology, East China University of Science and Technology, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Lantian
authors.initials: L
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Yi
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases