DOI: 10.1083/jcb.200206049. PTPα regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration

PTPα regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration

10.1083/jcb.200206049

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

We investigated the molecular and cellular actions of receptor protein tyrosine phosphatase (PTP) α in integrin signaling using immortalized fibroblasts derived from wild-type and PTPα-deficient mouse embryos. Defects in PTPα−/− 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 PTPα−/− cells was increased by expression of active (but not inactive) PTPα. Integrin-mediated formation of src–FAK and fyn–FAK complexes was reduced or abolished in PTPα−/− cells on FN, concomitant with markedly reduced phosphorylation of FAK at Tyr397. Reintroduction of active (but not inactive) PTPα restored FAK Tyr-397 phosphorylation. FN-induced cytoskeletal rearrangement was retarded in PTPα−/− 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 PTPα−/− fibroblasts (Ponniah et al., 1999; Su et al., 1999), suggest that PTPα functions in integrin signaling and cell migration as an Src-PTK activator. Our paper establishes that PTPα is required for early integrin-proximal events, acting upstream of FAK to affect the timely and efficient phosphorylation of FAK Tyr-397.

Bibliography

Zeng, L., Si, X., Yu, W.-P., Le, H. T., Ng, K. P., Teng, R. M. H., Ryan, K., Wang, D. Z.-M., Ponniah, S., & Pallen, C. J. (2003). PTPÎ± regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. The Journal of Cell Biology, 160(1), 137â146.

Authors 10

Li Zeng (first)
Xiaoning Si (additional)
Wei-Ping Yu (additional)
Hoa Thi Le (additional)
Kwok Peng Ng (additional)
Raymond M.H. Teng (additional)
Kenneth Ryan (additional)
Dennis Z.-M. Wang (additional)
Sathivel Ponniah (additional)
Catherine J. Pallen (additional)

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Dates

Type	When
Created	22 years, 7 months ago (Jan. 6, 2003, 2:04 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 10 a.m.)
Indexed	1 week, 2 days ago (Aug. 19, 2025, 6:02 a.m.)
Issued	22 years, 7 months ago (Jan. 6, 2003)
Published	22 years, 7 months ago (Jan. 6, 2003)
Published Online	22 years, 7 months ago (Jan. 6, 2003)
Published Print	22 years, 7 months ago (Jan. 6, 2003)

Funders 0

None

BibTeX

@article{Zeng_2003, title={PTPα regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration}, volume={160}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200206049}, DOI={10.1083/jcb.200206049}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Zeng, Li and Si, Xiaoning and Yu, Wei-Ping and Le, Hoa Thi and Ng, Kwok Peng and Teng, Raymond M.H. and Ryan, Kenneth and Wang, Dennis Z.-M. and Ponniah, Sathivel and Pallen, Catherine J.}, year={2003}, month=jan, pages={137–146} }

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