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
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
October 2005
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), .
(doi:10.1242/?jcs.02615).
(PMID:16219691)
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.
This record has no associated files available for download.
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
Catalogue record
Date deposited: 22 Aug 2014 10:13
Last modified: 15 Mar 2024 03:50
Export record
Altmetrics
Contributors
Author:
Michael C. Brown
Author:
Sara E. Hetey
Author:
Christopher E. Turner
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
