Prickett TD and Brautigan DL (2006) The alpha4 regulatory subunit exerts opposing allosteric effects on protein phosphatases PP6 and PP2A. J Biol Chem 281(41):30503-11
Abstract: The protein Ser/Thr phosphatase family contains three enzymes called PP2A, PP4 and PP6 with separate biological functions inferred from genetics of the yeast homologues Pph21/22, Pph3, and Sit4. These catalytic subunits associate with a common subunit called alpha-4 (related to yeast Tap42). Here, we characterized recombinant PP6 and PP2A catalytic monomers and alpha-4::phosphatase heterodimers. Monomeric PP6 and PP2A showed identical kinetics using either p-nitrophenyl phosphate (pNPP) or 32P-myelin basic protein (MBP) as substrates, with matching KM and Vmax values. Using pNPP as substrate PP6 and PP2A gave the same IC50 with active site inhibitors okadaic acid, microcystin-LR, calyculin A, and cantharidin. However, with MBP as substrate PP6 was inhibited at 5-fold lower concentrations of toxins relative to PP2A, suggesting PP6 might be a preferred in vivo target of toxins. Heterodimeric alpha-4::PP6 and alpha-4::PP2A were starkly different. With MBP as substrate the alpha-4::PP2A heterodimer had a 100-fold higher Vmax than alpha-4::PP6 and neither heterodimer was active with pNPP. Thus, these phosphatases are distinguished by their different responses to allosteric binding of the common regulatory subunit alpha-4. Transient expression of alpha-4 differentially increased or decreased phosphorylation of endogenous phosphoproteins, consistent with opposing effects on PP2A and PP6.
|Status: Published||Type: Journal Article||PubMed ID: 16895907|
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