Low molecular weight protein tyrosine phosphatases: small,but smart |
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Authors: | Raugei G Ramponi G Chiarugi P |
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Institution: | (1) Dipartimento di Scienze Biochimiche, Viale Morgagni 50, 50134 Firenze (Italy), Fax + 39 055 4222725, e-mail: ramponi@scibio.unifi.it, IT |
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Abstract: | Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are a family of 18-kDa enzymes involved in cell growth regulation.
Despite very limited sequence similarity to the PTP superfamily, they display a conserved signature motif in the catalytic
site. LMW-PTP associates and dephosphorylate many growth factor receptors, such as platelet-derived growth factor receptor
(PDGF-r), insulin receptor and ephrin receptor, thus downregulating many of the tyrosine kinase receptor functions that lead
to cell division. In particular, LMW-PTP acts on both growth-factor-induced mitosis, through dephosphorylation of activated
PDGF-r, and on cytoskeleton rearrangement, through dephosphorylation of p190RhoGAP and the consequent regulation of the small
GTPase Rho. LMW-PTP activity is modulated by tyrosine phosphorylation on two specific residues, each of them with specific
characteristics. LMW-PTP activity on specific substrates depends also on its localization. Moreover, LMW-PTP is reversibly
oxidized during growth factor signaling, leading to inhibition of its enzymatic activity. Recovery of phosphatase activity
depends on the availability of reduced glutathione and involves the formation of an S–S bridge between the two catalytic site
cysteines. Furthermore, studies on the redox state of LMW-PTP in contact-inhibited cells and in mature myoblasts suggest that
LMW-PTP is a general and versatile modulator of growth inhibition.
Received 17 January 2002; received after revision 22 March 2002; accepted 26 March 2002 |
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Keywords: | : PTP LMW-PTP redox regulation PDGF-r cytoskeleton rearrangement growth inhibition |
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