Protein phosphatase-1 (PP1) associates with various regulatory subunits that dictate its subcellular localization
and modulate its substrate specificity.
Phosphorylation of serine and threonine residues in proteins is a crucial step in the regulation of many cellular functions
ranging from hormonal regulation to cell division and even short-term memory. The level of phosphorylation is controlled by
the opposing actions of protein kinases and protein phosphatases. Protein phosphatase 1 (PP1) is 1 of 4 major
serine/threonine-specific protein phosphatases which have been identified in eukaryotic cells by enzymatic methods.
Although the 4 have overlapping substrate specificities in vitro, they can be distinguished by the use of inhibitor proteins and
by their dependence on metal ions.
NCBI Summary:
This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system. The encoded protein has putative tumor suppressor function and decreased expression has been observed in tumors. [provided by RefSeq, Feb 2014]
General function
Intracellular signaling cascade
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Cellular localization
Cytoplasmic
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Ovarian function
Steroid metabolism, Luteinization
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How Protein Kinase A Activates Canonical Tyrosine Kinase Signaling Pathways to Promote Granulosa Cell Differentiation. [Law NC et al. (2017)$28460125] Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation. For both pathways, PKA initiates signaling by regulating the activity of a protein phosphatase. For the PI3K/AKT pathway, PKA activates the Ser/Thr protein phosphatase PP1 complexed with the insulin-like growth factor 1 receptor (IGF1R) and insulin receptor substrate 1 (IRS1) to dephosphorylate Ser residues on IRS1, authorizing phosphorylation of IRS1 by the IGF1R to activate PI3K. Treatment of GCs with FSH and exogenous IGF1 initiates synergistic IRS1 Tyr phosphorylation and resulting gene activation. The mechanism by which PKA activates PI3K is conserved in preovulatory GCs, MCF7 breast cancer cells, and FRTL thyroid cells. For the MAPK/ERK pathway, PKA promotes inactivation of the MAPK phosphatase (MKP) dual specificity phosphatase (DUSP) MKP3/DUSP6 to permit MEK-phosphorylated ERK to accumulate downstream of the epidermal growth factor receptor. Thus, for the two central signaling pathways that regulate gene expression in GCs, FSH via PKA intersects canonical RTK-regulated signaling by modulating the activity of protein phosphatases.//////////////////
Gonzalez Reyes J, et al. reported effects of the protein phosphatase inhibitor okadaic acid on FSH-induced granulosa cell steroidogenesis. They concluded that type 1 and 2A serine/threonine protein phosphatases (PP1 and PP2A) may be important in regulating the phosphorylation state of proteins
implicated in the cAMP-protein kinase A-stimulated steroidogenic activity of granulosa cells.
Expression regulated by
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Ovarian localization
Granulosa, Luteal cells
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Polyclonal antibodies raised against the catalytic subunits of PP types 1 and 2A, and a monoclonal antibody raised against
the Ca(2+)-binding subunit of PP2B, were used by Ford SL,et al to identify immunoreactive proteins that migrated on SDS-PAGE with
approximate molecular masses of 37, 34 and 16 kDa, corresponding well with the reported molecular mass of PP1, PP2A and PP2B respectively. Five selective inhibitors of PP1/PP2A: okadaic acid, calyculin A, cantharidin, tautomycin and
microcystin-RR, each caused a dose-dependent decrease in the activity of PPs in luteal cell homogenates, and also enhanced
32P incorporation into numerous luteal cell proteins; most notably, proteins with approximate molecular masses of 20 and 22
kDa. The results of this study suggest that PPs may play an important role in the regulation of rat luteal cell functions.
Follicle stages
Antral, Preovulatory, Corpus luteum
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Eyster KM, et al. reported protein phosphatase activity in the rat ovary throughout pregnancy and pseudopregnancy.