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Protein phosphatases. Protein phosphatase acting as a reset button for kinases this action is either a) inactivating or b) activating. like for protein kinases, a distinction is made between tyrosine and threonine /serine phosphatases.
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Protein phosphatase acting as a reset button for kinasesthis action iseithera) inactivatingorb) activating
like for protein kinases, a distinction is made between tyrosine and threonine/serine phosphatases As there is always an exception to the rule: certain phosphatases recognize both phosphotyrosine and phosphothreonine/serine residues these are the dual specificity phosphatases
{ serine threonine { tyrosine serine threonine tyrosine {
The depth of the catalyticpocketis one of the determinants of phosphoresiduespecificity of the protein phosphatase
Mechanism of action and highlyconserved (signature) sequences of serine / threonineprotein phosphatases. The catalyticsubunits have broadspecificity
Specificity of serine/threonine phosphatases islargelydetermined by association of regulatorysubunitsthat affect subcellular localisation as well as substratespecificity
The regulatorysubunit MYPT1 turns the broad-specificity PP1C (catalyticsubunit) into a myosinregulatory-light chain-specific phosphatase - R= arginine & K= lysine are positivelychargedresiduesthat fit the negativelychargedacidic groove - Dephosphorylation of myosinregulatorylight chaincauses smooth muscle cell relaxation (no hydrolysis of ATP)
Role of the phosphatase calcineurin in antigen-mediated T-cell activation(followed by clonal expansion (adaptive immunity))
the activated T-cellreceptorinduces a Ca2+ signal thatbindscalcineurin and activates the catalyticsubunit (CnA) (PP2B), leading to dephosphorylation and nuclear translocation of the transcription factor NFAT NFAT=nuclear factor of activated T-cells
Tyrosine phosphatase as an inactivator of insulinsignalling: tyrosine phosphatase 1B (PTP1B) dephosphorylates the insulinreceptor
Certain tyrosine phosphatases have tumoursuppressorfunctions (by opposing to deragulated tyrosine protein kinases)
tyrosine phosphatase as an activator of Src: dephosphorylation of the C-terminal tyrosine phosphate by CD45
the SH2 domainbound to the C-terminal phosphotyrosinekeeps the kinase in an incompetent conformation dephosphorylationremovesthisconstraint and isfollowed by autophosphorylation. The kinase isnowfullycompetent
PTEN qualifies by its structure and itssequence as a tyrosine phosphatase but itprefersinositollipidsand acts as a inositollipid phosphatase (important tumoursuppressorrole)
PTEN removes the phosphates that have been added by PI 3-kinase PI 3-kinase isactivated by growthfactors (includinginsulin) and plays an important role in growthregulation and cellsurvival thisexplainswhyloss of PTEN isinvolved in cell transformation (cancer development)