Protein tyrosine phosphatases and the control of cellular signaling responses

Tonks, N. K. (1996) Protein tyrosine phosphatases and the control of cellular signaling responses. Advances in Pharmacology, 36. pp. 91-119. ISSN 1054-3589 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8783556
DOI: 10.1016/S1054-3589(08)60578-5

Abstract

It is important to realize that in vivo protein tyrosine phosphorylation is a reversible, dynamic process in which the net level of phosphate in a target substrate reflects not only the activity of the PTKs that phosphorylate it, but also the competing action of the protein tyrosine phosphatases (PTPs) that catalyze the dephosphorylation reaction. One of the major technical difficulties that held back the study of PTPs was the requirement for a suitably phosphorylated purified protein substrate with which to measure enzyme activity. This was a particularly acute problem for the PTPs because at this time their physiological substrates were either not yet clearly identified or unavailable in the quantity required for routine assays. The development of this substrate gave us the means to assay PTP activity over a broad range of substrate concentrations. It also enabled us to exploit the ability of the insulin receptor PTK to utilize ATPγS as a phosphate donor and thus to generate a highly thiophosphorylated derivative of RCM lysozyme. Because tyrosine phosphorylation has been implicated in promoting cell growth and proliferation, PTPs, as the natural antagonists of PTK function, may exert a negative effect on such growth-promoting signals by triggering net dephosphorylation of proteins in the membrane. The advantage of the involvement of receptor PTPs in such a phenomenon is that their extracellular segments may “sense” cell-cell contact directly.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Ca(2+)-Calmodulin Dependent Protein Kinase/antagonists & inhibitors/metabolism Cell Adhesion Cell Cycle Proteins Growth Inhibitors/metabolism Immediate-Early Proteins/metabolism/physiology Models, Molecular Molecular Sequence Data Phosphoprotein Phosphatase Phosphorylation Protein-Tyrosine-Phosphatase/chemistry/metabolism/ physiology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Signal Transduction/ physiology Xenopus laevis src Homology Domains
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
organs, tissues, organelles, cell types and functions > tissues types and functions > signal transduction
organism description > animal > Frog > xenopus
CSHL Authors:
Communities: CSHL labs > Tonks lab
Depositing User: Kathleen Darby
Date: 1996
Date Deposited: 13 May 2014 14:44
Last Modified: 13 May 2014 14:44
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30118

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