Serine/threonine protein phosphatases in the control of cell function

Anna A. Depaoli-Roach, In Kyung Park, Vaclav Cerovsky, Csilla Csortos, Stephen D. Durbin, Martha J. Kuntz, Albert Sitikov, Pauline M. Tang, Alexander Dmitriyevich Verin, Stanislaw Zolnierowicz

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Abstract

Reversible protein phosphorylation is a fundamental mechanism by which many biological functions are regulated. Achievement of such control requires the coordinated action of the interconverting enzymes, the protein kinases and protein phosphatases. By comparison with protein kinases, a limited number of protein phosphatase catalytic subunits are present in the cell, which raises the question of how such a small number of dephosphorylating enzymes can counterbalance the action of the more numerous protein kinases. In mammalian cells, four major classes of Ser/Thr-specific phosphatase catalytic subunits have been identified, comprising two distinct gene families. The high degree of homology among members of the same family, PP1, PP2A and PP2B, and the high degree of evolutionary conservation between organisms as divergent as mammals and yeast, implies that these enzymes are involved in fundamental cell functions. Type 1 enzymes appear to acquire specificity by association with targeting regulatory subunits which direct the enzymes to specific cellular compartments, confer substrate specificity and control enzyme activity. In spite of the progress made in determining the structure of the PP2A subunits, very little is known about the control of this activity and about substrate selection. Recent studies have unravelled a significant number of regulatory subunits. The potential existence of five distinct B or B-related polypeptides, some of which are present in multiple isoforms, two A and two C subunit isoforms, raises the possibility that a combinatorial association could generate a large number of specific PP2A forms with different substrate specificity and/or cellular localization. Moreover, biochemical, biological and genetic studies all concur in suggesting that the regulatory subunits may play an important role in determining the properties of the Ser/Thr protein phosphatases and hence their physiological functions.

Original languageEnglish (US)
Pages (from-to)199-224
Number of pages26
JournalAdvances in Enzyme Regulation
Volume34
Issue numberC
DOIs
StatePublished - Jan 1 1994

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Phosphoprotein Phosphatases
Enzymes
Protein Kinases
Substrate Specificity
Catalytic Domain
Protein Isoforms
Phosphoric Monoester Hydrolases
Molecular Biology
Mammals
Yeasts
Phosphorylation
Peptides
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Depaoli-Roach, A. A., Park, I. K., Cerovsky, V., Csortos, C., Durbin, S. D., Kuntz, M. J., ... Zolnierowicz, S. (1994). Serine/threonine protein phosphatases in the control of cell function. Advances in Enzyme Regulation, 34(C), 199-224. https://doi.org/10.1016/0065-2571(94)90017-5

Serine/threonine protein phosphatases in the control of cell function. / Depaoli-Roach, Anna A.; Park, In Kyung; Cerovsky, Vaclav; Csortos, Csilla; Durbin, Stephen D.; Kuntz, Martha J.; Sitikov, Albert; Tang, Pauline M.; Verin, Alexander Dmitriyevich; Zolnierowicz, Stanislaw.

In: Advances in Enzyme Regulation, Vol. 34, No. C, 01.01.1994, p. 199-224.

Research output: Contribution to journalArticle

Depaoli-Roach, AA, Park, IK, Cerovsky, V, Csortos, C, Durbin, SD, Kuntz, MJ, Sitikov, A, Tang, PM, Verin, AD & Zolnierowicz, S 1994, 'Serine/threonine protein phosphatases in the control of cell function', Advances in Enzyme Regulation, vol. 34, no. C, pp. 199-224. https://doi.org/10.1016/0065-2571(94)90017-5
Depaoli-Roach AA, Park IK, Cerovsky V, Csortos C, Durbin SD, Kuntz MJ et al. Serine/threonine protein phosphatases in the control of cell function. Advances in Enzyme Regulation. 1994 Jan 1;34(C):199-224. https://doi.org/10.1016/0065-2571(94)90017-5
Depaoli-Roach, Anna A. ; Park, In Kyung ; Cerovsky, Vaclav ; Csortos, Csilla ; Durbin, Stephen D. ; Kuntz, Martha J. ; Sitikov, Albert ; Tang, Pauline M. ; Verin, Alexander Dmitriyevich ; Zolnierowicz, Stanislaw. / Serine/threonine protein phosphatases in the control of cell function. In: Advances in Enzyme Regulation. 1994 ; Vol. 34, No. C. pp. 199-224.
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