Phosphatases cell functions

Other phosphatases have also been identified and may be implicated in mitotic and meiotic germ cell functions. For example, INH was originally isolated from a Xenopus oocyte cell free system as an inhibitor of pre-MPF activity (Cyert and Kirschner, 1988). INH encodes a protein phosphatase 2Athat negatively regulates MPF activity by dephosphory-lating Cdc2 on thr-161 (Lee et al., 1991 Solomon et al., 1990). 

Protein serine-threonine phosphatases play a critical role in the control of cell function 400... 

N.K. Tonks, and B.G. Neel, From form to function Signaling by protein tyrosine phosphatases. Cell 87(1996)365-368. 

The importance of sHsp phosphorylation for in vivo protection of cell function has been conflicting, potentially reflecting different cellular requirements for the activities of oligomeric and dissociated sHsps in different cell types (Rogalla etal., 1999). The difference in the effect of phosphorylation on chaperone activity in vitro is more difficult to explain. Rogalla and colleagues (1999) report phosphorylation inhibits chaperone activity, while previous reports indicated it had no effect (Knauf et al., 1994). One possibility is that the earlier sHsp preparations were contaminated with phosphatases that removed the phosphates prior to the assay. 

Mechanism of action These peptide antibiotics interfere with T cell function by binding to immunophyllins, small cytoplasmic proteins that play critical roles in T cell responses to TCR activation and to cytokines. Cyclosporine binds to cyclophilin and tacrolimus binds to FK-binding protein (FKBP), both complexes inhibiting calcineurin, a cytoplasmic phosphatase. Calcineurin regulates the ability of the nuclear factor of activated T cells (NF-AT) to translocate to the nucleus and increase the production of cytokines. Cyclophilin and tacrolimus both inhibit the production of cytokines that normally occurs in response to TCR activation. Sirolimus also binds to FKBP, inhibiting the re-... 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

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