Phosphatase Regulator Proteins


 Creative BioMart Phosphatase Regulator Proteins Product List
 Phosphatase Regulator Proteins Background

Phosphorylation and dephosphorylation of proteins were described by Edmond Fischer and Edwin Krebs over four decades ago and their seminal contributions to research in this area were recognized in 1992 with a Nobel Prize. The process of reversible phosphorylation now is recognized as a universal mechanism for the post-translational control of protein function. All physiological processes are subject to this type of regulation, including, transcription, translation, ion transport, cell structure, motility, mitosis and cell cycle progression.

The dephosphoiylation of proteins on their serine, threonine and tyrosine residues is catalyzed by three families of protein phosphatases that regulate numerous intracellular processes. Diversity of structure within a family is generated by targeting the regulatory subunits and domains. Structural studies of these enzymes have revealed that although two families of protein serine/threonine phosphatases are unrelated in sequence, the architecture of their catalytic domains is remarkably similar and distinct from the protein tyrosine phosphatases.

Reversible protein phosphorylation is a critical component of the signal transduction mechanisms by which extracellular signals regulate homeostasis and cell growth. Extracellular effectors act by modulating protein kinases and protein phosphatases, which catalyze the opposing activities of protein phosphorylation and dephosphorylation, respectively. Change in the phosphorylation state of proteins on their serine, threonine and tyrosine residues are responsible for disparate protein confirmational and hence functional changes, and this, together with its reversibility and scope for signal amplification, probably accounts for the importance of protein phosphorylation in signal transduction.

Protein phosphatases (PPs) are structurally and functionally diverse enzymes which are represented by three distinct gene families. Two of these, the PPP and PPM families, dephosphorylate phosphoserine and phosphothreonine residues, whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine. The most abundant protein serine/ threonine phosphatases of the eukaryotes, PP1, PP2A and PP2B, belong to the PPP family whereas PP2C and the related mitochondrial pyruvate dehydrogenase phosphatase are members of the PPM family. Within each family, although the catalytic domains are highly conserved, suggesting similarities in tertiary structure and catalytic mechanisms, considerable structural and functional diversity of individual protein phosphatases is created as a result of a combination of associated regulatory domains and subunits.

Protein serine/threonine phosphatases of the PPP family play numerous roles in mediating intracellular signaling processes. In addition to PP1, PP2A and PP2B, related novel protein phosphatases have recently been characterized that occur in low abundance and in a tissue and developmental specific manner. PP1 and PP2A are specifically inhibited by a variety of naturally occurring toxins such as okadaic acid, a diarrhetic shellfish poison and strong tumor promotor, and microcystin, a liver toxin produced by blue green algae. Whereas PP2B is only poorly inhibited by the toxins that affect PP1 and PP2A, it was recently defined as the immunosuppressive target of FK506 and cyclosporin in association with their major cellular binding proteins, the cis-trans peptidyl propyl isomerases FKBP12 and cyclophilin, respectively. The structural complexity of PP1 and PP2 holoenzymes in vivo resolves the seemingly paradoxical situation that a relatively small number of protein phosphatase catalytic subunits are responsible for the specific dephosphoiylation of a variety of cellular proteins, and that both PP 1 and PP2A have been implicated in regulating many diverse cellular functions, including glycogen metabolism, muscle contraction, control of the cell cycle and RNA splicing. As the individual catalytic subunits of PP 1 and PP2A catalyze the dephosphoiylation of a broad and overlapping range of substrates in vitro, specificity in vivo is generated either by altering the selectivity of the enzyme towards a particular substrate or by targeting the phosphatase to the subcellular location of its substrates. This is achieved by regulatory or targeting subunits that bind to the phosphatase catalytic subunits. In addition, the regulatory subunits allow the activity of the PPPs to be modulated by reversible protein phosphorylation and second messengers.