Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells

Jarrett E Walsh; M Rita I Young

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Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells

Journal article

Peer reviewed

Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells

Jarrett E Walsh and M Rita I Young

Anticancer research, Vol.30(12), pp.4861-4866

12/2010

PMCID: PMC3337686

PMID: 21187463

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Abstract

Motility of endothelial cells is a requirement for the vascularization of solid malignancies. While tumors have been shown to produce a host of angiogenic factors, including TGF-β, the mechanisms by which such factors regulate endothelial cell motility have not yet been defined. Thus, the role of the serine/threonine phosphatase PP-1 in regulating endothelial cell motility and cytoskeletal architecture was studied. The present study demonstrated that TGF-β stimulation of motility is dependent on PP-1. Likewise, TGF-β was shown to up-regulate paxillin expression through a process that was PP-1 dependent. The interplay between PP-1 and TGF-β was further observed by the induction of cell rounding and the loss of paxillin-actin co precipitations upon PP-1 inhibition and the compensation for these effects by TGF-β. Studies initiated to determine how PP-1 might regulate motility showed its role in maintaining cytoskeletal organization and its capacity to directly dephosphorylate the focal adhesion scaffolding protein paxillin. These studies suggest that the interplay between TGF-β and PP-1 regulates the motility of endothelial cells that is critical to the process of angiogenesis.

Actins - metabolism

Animals

Carcinoma, Lewis Lung - blood supply

Carcinoma, Lewis Lung - metabolism

Carcinoma, Lewis Lung - pathology

Cell Movement - drug effects

Cell Movement - physiology

Culture Media, Conditioned

Cytoskeleton - drug effects

Cytoskeleton - metabolism

Cytoskeleton - pathology

Endothelial Cells - drug effects

Endothelial Cells - metabolism

Endothelial Cells - pathology

Focal Adhesions - drug effects

Furans - pharmacology

Humans

Lipids - pharmacology

Mice

Paxillin - biosynthesis

Paxillin - metabolism

Phosphorylation

Protein Phosphatase 1 - antagonists & inhibitors

Protein Phosphatase 1 - metabolism

Protein Phosphatase 1 - physiology

Transforming Growth Factor beta - metabolism

Transforming Growth Factor beta - pharmacology

Transforming Growth Factor beta - physiology

Up-Regulation - drug effects

Details

Title: Subtitle: Interrelationship between protein phosphatase 1 and TGF-{beta} in regulating motility and cytoskeletal architecture of endothelial cells
Creators: Jarrett E Walsh - Ralph H. Johnson VA Medical Center
M Rita I Young
Resource Type: Journal article
Publication Details: Anticancer research, Vol.30(12), pp.4861-4866
PMID: 21187463
PMCID: PMC3337686
eISSN: 1791-7530
Grant note: R01 CA128837 / NCI NIH HHS R01 CA097813-05 / NCI NIH HHS R01CA128837 / NCI NIH HHS R01 CA045080-14 / NCI NIH HHS R01 CA097813 / NCI NIH HHS R01 DE018168-04 / NIDCR NIH HHS R01 DE018168 / NIDCR NIH HHS
Language: English
Date published: 12/2010
Academic Unit: Otolaryngology
Record Identifier: 9984311441402771

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