title: SHP-2 inhibits tyrosine phosphorylation of Cas-L and regulates cell migration.
abstract: The Src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SHP-2, plays an important role in cell migration by interacting with various proteins. In this report, we demonstrated that SHP-2 inhibits tyrosine phosphorylation of Crk-associated substrate lymphocyte type (Cas-L), a docking protein which mediates cell migration, and found that SHP-2 negatively regulates migration of A549 lung adenocarcinoma cells induced by fibronectin (FN). We showed that overexpressed SHP-2 co-localizes with Cas-L at focal adhesions and that exogenous expression of SHP-2 abrogates cell migration mediated by Cas-L. SHP-2 inhibits tyrosine phosphorylation of Cas-L, and associates with Cas-L to form a complex in a tyrosine phosphorylation-dependent manner. Finally, immunoprecipitation experiments with deletion mutants revealed that both SH2 domains of SHP-2 are necessary for this association. These results suggest that SHP-2 regulates tyrosine phosphorylation of Cas-L, hence opposing the effect of kinases, and SHP-2 is a negative regulator of cell migration mediated by Cas-L.
authors.affiliation: Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kondo
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nomura
authors.forename: Osamu
authors.initials: O
authors.lastname: Hosono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D014443:Tyrosine; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11