title: Kindlin-2 phosphorylation by Src at Y193 enhances Src activity and is involved in Migfilin recruitment to the focal adhesions.
abstract: Kindlin-2 regulates external to internal cell signaling by interaction with integrins in a process that involves the tyrosine kinase, Src. However, the underlying mechanisms remain elusive. Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration. These findings suggest that Src, Kindlin-2 and Migfilin together constitute a positive feedback loop that controls Src activity and regulates integrin-mediated cellular functions.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Danyu
authors.initials: D
authors.lastname: Lu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Junhu
authors.initials: J
authors.lastname: Wan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China. Electronic address: Hongquan.Zhang@bjmu.edu.cn.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human; C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019061:src-Family Kinases
keywords: Focal adhesion; Kindlin-2; Migfilin; Src; Tyrosine phosphorylation