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Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker

Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker
Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker
The tyrosine phosphatase PTP-PEST has been implicated in the regulation of cell spreading and migration through dephosphorylation of focal adhesion proteins and inhibition of Rac GTPase activity. The focal adhesion adaptor protein paxillin is also necessary for normal cell migration and binds directly to PTP-PEST. In this study, we have utilized PTP-PEST(-/-) and paxillin(-/-) fibroblasts to demonstrate that paxillin is essential for PTP-PEST inhibition of cell spreading and membrane protrusion as well as inhibition of adhesion-induced Rac activation. Furthermore, we show that paxillin-binding is necessary for PTP-PEST stimulation of cell migration. Mutation analysis indicates that PTP-PEST function involves binding to the paxillin C-terminal LIM domains, and signaling through the tyrosine 31 and 118 phosphorylation sites, as well as the LD4 motif of the paxillin N-terminus. Using 'substrate trapping' approaches and immunoprecipitation, we show that the ARF GAP paxillin kinase linker PKL/GIT2, a paxillin LD4 binding partner, is a substrate for PTP-PEST. Additionally, the PKL-paxillin interaction was necessary for PTP-PEST inhibition of cell spreading. These data provide mechanistic insight into how the paxillin-PTP-PEST interaction contributes to integrin signaling events associated with the spatiotemporal regulation of key modulators of the cytoskeleton and cell motility machinery.
rac, cytoskeleton, phosphatase, focal adhesions, tyrosine phosphorylation, cell migration
0021-9533
5835-5847
Jamieson, Jennifer S.
f34ba87f-4ec3-472d-b8a3-74eff08c647f
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Hallé, Maxime
ea1c4e07-083a-4060-a702-d823f782f728
Brown, Michael C.
3f7046eb-5b0e-4813-8537-a8e1b09c611e
Tremblay, Michel L.
6dc24563-0597-494b-8f41-4badab9a2403
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850
Jamieson, Jennifer S.
f34ba87f-4ec3-472d-b8a3-74eff08c647f
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Hallé, Maxime
ea1c4e07-083a-4060-a702-d823f782f728
Brown, Michael C.
3f7046eb-5b0e-4813-8537-a8e1b09c611e
Tremblay, Michel L.
6dc24563-0597-494b-8f41-4badab9a2403
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850

Jamieson, Jennifer S., Tumbarello, David A., Hallé, Maxime, Brown, Michael C., Tremblay, Michel L. and Turner, Christopher E. (2005) Paxillin is essential for PTP-PEST-dependent regulation of cell spreading and motility: a role for paxillin kinase linker. Journal of Cell Science, 118 (24), 5835-5847. (doi:10.1242/?jcs.02693). (PMID:16317044)

Record type: Article

Abstract

The tyrosine phosphatase PTP-PEST has been implicated in the regulation of cell spreading and migration through dephosphorylation of focal adhesion proteins and inhibition of Rac GTPase activity. The focal adhesion adaptor protein paxillin is also necessary for normal cell migration and binds directly to PTP-PEST. In this study, we have utilized PTP-PEST(-/-) and paxillin(-/-) fibroblasts to demonstrate that paxillin is essential for PTP-PEST inhibition of cell spreading and membrane protrusion as well as inhibition of adhesion-induced Rac activation. Furthermore, we show that paxillin-binding is necessary for PTP-PEST stimulation of cell migration. Mutation analysis indicates that PTP-PEST function involves binding to the paxillin C-terminal LIM domains, and signaling through the tyrosine 31 and 118 phosphorylation sites, as well as the LD4 motif of the paxillin N-terminus. Using 'substrate trapping' approaches and immunoprecipitation, we show that the ARF GAP paxillin kinase linker PKL/GIT2, a paxillin LD4 binding partner, is a substrate for PTP-PEST. Additionally, the PKL-paxillin interaction was necessary for PTP-PEST inhibition of cell spreading. These data provide mechanistic insight into how the paxillin-PTP-PEST interaction contributes to integrin signaling events associated with the spatiotemporal regulation of key modulators of the cytoskeleton and cell motility machinery.

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More information

Published date: December 2005
Keywords: rac, cytoskeleton, phosphatase, focal adhesions, tyrosine phosphorylation, cell migration
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 362402
URI: http://eprints.soton.ac.uk/id/eprint/362402
ISSN: 0021-9533
PURE UUID: ccc0a778-553f-4e4a-bd85-66facc277bcb
ORCID for David A. Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561

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Date deposited: 22 Aug 2014 09:01
Last modified: 20 Jul 2019 00:37

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Contributors

Author: Jennifer S. Jamieson
Author: Maxime Hallé
Author: Michael C. Brown
Author: Michel L. Tremblay
Author: Christopher E. Turner

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