Physiological Reviews, Vol 73, 673-699, Copyright © 1993 by American Physiological Society
Protein serine/threonine phosphatases: structure, regulation, and functions in cell growth
M. C. Mumby and G. Walter
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas.
It is clear that much remains to be discovered regarding the roles of
protein phosphatases in mitogenic signaling pathways. The ability of
okadaic acid to activate MAPK/ERKs demonstrates that alteration in
serine/threonine dephosphorylation can have significant effects on common
steps in growth stimulation induced by different types of mitogens. As in
the case of cell cycle control, protein serine/threonine phosphatase plays
a central role in the reentry of quiescent cells into the cycle. Because
the only known targets of okadaic acid are the catalytic subunits PP1 and
PP2A, these enzymes are crucial components of two basic functions carried
out by cells: growth and division. Important and obligatory roles for PP2B,
PP2C, and newly discovered serine/threonine phosphatases are also likely.
However, the limited tissue distribution, unique regulatory properties, and
limited substrate specificities of these forms suggest more specialized
functions in restricted cell types. The available information on the
specific functions of different forms of protein serine/threonine
phosphatases, let alone their individual isoforms and different multimeric
holoenzymes, is still severely limited. Years of biochemical
characterization and cDNA cloning have left us with far more forms than
functions. This has led to the gratifying situation, at least for the
biochemists, in which genetics and cell biology identify protein
phosphatases for which a wealth of biochemical information is already
available. The appreciation of the importance of these enzymes in the
coming years can only increase as the functions for individual forms are
discovered.
