s a cytoplasmic protein that
contains a phosphatase-catalytic domain in the carboxyl terminal region and 2 tandemly repeated, src-homology 2
(SH2) domains in the amino terminal region. SH2 domains were first identified in the SRC gene family and found in a
variety of proteins involved in signal transduction. The SH2 domains may recognize phosphorylated tyrosine residues
and direct protein-protein associations.
NCBI Summary:
The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Three alternatively spliced variants of this gene, which encode distinct isoforms, have been reported.
General function
Intracellular signaling cascade, Transferase
Comment
Cellular localization
Cytoplasmic, Nuclear
Comment
Ovarian function
Follicle atresia, Luteinization
Comment
Expression regulated by
FSH, Steroids, prolactin
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Russell DL, et al 1999 reported the differentiation-dependent prolactin responsiveness and stat (signal transducers and activators of transcription) signaling in rat ovarian cells.
PRL activates an important cytokine signaling cascade that is obligatory for maintaining luteal cell function in the rat ovary. To determine when specific components of this cascade are expressed and can be activated by PRL, the auhors analyzed the expression of receptor subtypes (short, PRL-R-S, and long, PRL-R-L), the presence and kinetics of Stat (signal transducer and activator of transcription) activation using the PRL-response element (PRL-RE) of the alpha 2M (alpha 2-macroglobulin) gene, acid the content and hormonal regulation of three specific modulators of cytokine signaling; the tyrosine phosphatases (SHP-1 and SHP-2), and the protein inhibitor of activated Stat3 (PIAS-3). These components were analyzed in differentiating granulosa/luteal cells of hypophysectomized (H) rats and in corpora lutea of pregnant rats.
Despite the increased PRL-R-L expression in differentiated granulosa cells, PRL did not stimulate detectable activation of Stats. Rather PRL activation of Stat5, principally Stat5b, occurred in association with luteinization. In contrast, granulosa cells of untreated
immature and H rats contained a high level of DNA binding activity, which was shown to be comprised entirely of activated, phosphorylated Stat3. Treatment with estrogen and FSH reduced the amount of phosphorylated Stat3 and abolished its ability to bind DNA, an effect temporally related to increased PIAS-3.
Expression of SHP-1 (but not SHP-2) was also hormonally regulated; SHP-1 mRNA and protein were high in granulosa cells of H rats, decreased by estrogen and FSH, and subsequently increased dramatically with luteinization. Of particular note, SHP-1 was localized in cytoplasm of granulosa cells in atretic follicles but was distinctly nuclear in luteal cells, indicative of different functional roles.
Collectively, these results indicate that Stat3 and Stat5 are activated by distinct cytokine-signaling pathways modulated through differentiation-dependent transcriptional regulation of signaling pathway
components and mediate distinct functional processes in the rat ovary: early follicle growth and atresia vs. luteinization.