The University of Southampton
University of Southampton Institutional Repository

Regulation of paxillin family members during epithelial-mesenchymal transformation: a putative role for paxillin delta

Regulation of paxillin family members during epithelial-mesenchymal transformation: a putative role for paxillin delta
Regulation of paxillin family members during epithelial-mesenchymal transformation: a putative role for paxillin delta
Epithelial-mesenchymal transformation (EMT) and the resulting induction of cell motility are essential components of tissue remodeling during embryonic development and wound repair, as well as tumor progression to an invasive metastatic phenotype. Paxillin, a multi-domain adaptor and phosphoprotein has previously been implicated in integrin signaling and cell motility. In this report we characterize a novel paxillin gene product, paxillin delta, generated from an evolutionarily conserved internal translation initiation site within the full-length paxillin mRNA. Paxillin delta, which lacks the key phosphorylation sites Y31 and Y118 as well as the ILK and actopaxin binding LD1 motif, exhibits a restricted distribution to epithelial cell types and is downregulated during TGF-beta1-induced EMT of normal murine mammary gland (NMuMG) epithelial cells. Interestingly, Hic-5, a paxillin superfamily member, exhibits a reciprocal protein expression profile to paxillin delta. In addition, paxillin delta expression is maintained following NMuMG differentiation in a 3D collagen I gel while other focal adhesion components are downregulated. Paxillin delta protein expression coincided with reduced paxillin tyrosine phosphorylation in NMuMG cells and paxillin delta overexpression in CHO.K1 cells inhibited adhesion-mediated tyrosine phosphorylation of paxillin. Forced expression of paxillin delta in NMuMG cells suppressed cell migration whereas Hic-5 overexpression stimulated motility. Together our data support a role for paxillin delta as a naturally occurring functional antagonist of paxillin signaling potentially through suppression of a Crk-mediated pathway during processes associated with cell migration.
Cell migration actin cytoskeleton, focal adhesion, crk, tyrosine phosphorylation, hic-5
0021-9533
4849-4863
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Brown, Michael C.
3f7046eb-5b0e-4813-8537-a8e1b09c611e
Hetey, Sara E.
3c72832c-c5d4-44d0-865f-4c7f6156d637
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850
Tumbarello, David A.
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
Brown, Michael C.
3f7046eb-5b0e-4813-8537-a8e1b09c611e
Hetey, Sara E.
3c72832c-c5d4-44d0-865f-4c7f6156d637
Turner, Christopher E.
a6c1a6bf-91ae-4d92-9980-0534fb696850

Tumbarello, David A., Brown, Michael C., Hetey, Sara E. and Turner, Christopher E. (2005) Regulation of paxillin family members during epithelial-mesenchymal transformation: a putative role for paxillin delta. Journal of Cell Science, 118 (20), 4849-4863. (doi:10.1242/?jcs.02615). (PMID:16219691)

Record type: Article

Abstract

Epithelial-mesenchymal transformation (EMT) and the resulting induction of cell motility are essential components of tissue remodeling during embryonic development and wound repair, as well as tumor progression to an invasive metastatic phenotype. Paxillin, a multi-domain adaptor and phosphoprotein has previously been implicated in integrin signaling and cell motility. In this report we characterize a novel paxillin gene product, paxillin delta, generated from an evolutionarily conserved internal translation initiation site within the full-length paxillin mRNA. Paxillin delta, which lacks the key phosphorylation sites Y31 and Y118 as well as the ILK and actopaxin binding LD1 motif, exhibits a restricted distribution to epithelial cell types and is downregulated during TGF-beta1-induced EMT of normal murine mammary gland (NMuMG) epithelial cells. Interestingly, Hic-5, a paxillin superfamily member, exhibits a reciprocal protein expression profile to paxillin delta. In addition, paxillin delta expression is maintained following NMuMG differentiation in a 3D collagen I gel while other focal adhesion components are downregulated. Paxillin delta protein expression coincided with reduced paxillin tyrosine phosphorylation in NMuMG cells and paxillin delta overexpression in CHO.K1 cells inhibited adhesion-mediated tyrosine phosphorylation of paxillin. Forced expression of paxillin delta in NMuMG cells suppressed cell migration whereas Hic-5 overexpression stimulated motility. Together our data support a role for paxillin delta as a naturally occurring functional antagonist of paxillin signaling potentially through suppression of a Crk-mediated pathway during processes associated with cell migration.

Full text not available from this repository.

More information

Published date: October 2005
Keywords: Cell migration actin cytoskeleton, focal adhesion, crk, tyrosine phosphorylation, hic-5
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 362405
URI: http://eprints.soton.ac.uk/id/eprint/362405
ISSN: 0021-9533
PURE UUID: 395e8857-3222-4363-a8d0-ca3c4f27a33e
ORCID for David A. Tumbarello: ORCID iD orcid.org/0000-0002-5169-0561

Catalogue record

Date deposited: 22 Aug 2014 10:13
Last modified: 05 Nov 2019 01:36

Export record

Altmetrics

Contributors

Author: Michael C. Brown
Author: Sara E. Hetey
Author: Christopher E. Turner

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×