title: PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration.
abstract: We investigated the molecular and cellular actions of receptor protein tyrosine phosphatase (PTP) alpha in integrin signaling using immortalized fibroblasts derived from wild-type and PTP alpha-deficient mouse embryos. Defects in PTP alpha-/- migration in a wound healing assay were associated with altered cell shape and focal adhesion kinase (FAK) phosphorylation. The reduced haptotaxis to fibronectin (FN) of PTP alpha-/- cells was increased by expression of active (but not inactive) PTP alpha. Integrin-mediated formation of src-FAK and fyn-FAK complexes was reduced or abolished in PTP alpha-/- cells on FN, concomitant with markedly reduced phosphorylation of FAK at Tyr397. Reintroduction of active (but not inactive) PTP alpha restored FAK Tyr-397 phosphorylation. FN-induced cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed filamentous actin stress fiber assembly and focal adhesion formation. This mimicked the effects of treating wild-type fibroblasts with the src family protein tyrosine kinase (Src-PTK) inhibitor PP2. These results, together with the reduced src/fyn tyrosine kinase activity in PTP alpha-/- fibroblasts (Ponniah et al., 1999; Su et al., 1999), suggest that PTP alpha functions in integrin signaling and cell migration as an Src-PTK activator. Our paper establishes that PTP alpha is required for early integrin-proximal events, acting upstream of FAK to affect the timely and efficient phosphorylation of FAK Tyr-397.
authors.affiliation: Cell Regulation Laboratory, Institute of Molecular and Cell Biology, Singapore 117609, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Si
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yu
authors.forename: Hoa Thi
authors.initials: HT
authors.lastname: Le
authors.forename: Kwok Peng
authors.initials: KP
authors.lastname: Ng
authors.forename: Raymond M H
authors.initials: RM
authors.lastname: Teng
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ryan
authors.forename: Dennis Z-M
authors.initials: DZ
authors.lastname: Wang
authors.forename: Sathivel
authors.initials: S
authors.lastname: Ponniah
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Pallen
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D002448:Cell Adhesion; D002465:Cell Movement; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015151:Immunoblotting; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface; D014443:Tyrosine / Q000378:metabolism; D016596:Vinculin / Q000096:biosynthesis
chemical_list: D016895:Culture Media, Serum-Free; D005353:Fibronectins; D016023:Integrins; D011956:Receptors, Cell Surface; D016596:Vinculin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4