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General Comment |
Suppressor of cytokine signaling (SOCS) protein expression is induced by cytokines in a range of tissues, and they
appear to act in a negative feedback loop to regulate signal transduction. Members of the SOCS family are
characterized by a variable N-terminal sequence, a central SH2 domain, and a conserved C-terminal SOCS box. They
mediate their inhibitory functions through interactions with JAK (e.g., JAK3; OMIM 600173) kinases.
NCBI Summary:
The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene but some of the full length sequences are not known.
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Comment |
S. P. Tam, et al 2001 reported tissue-Specific Induction of SOCS Gene Expression by PRL.
The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that
expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is
increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating PRL and pups
for 24 h but not in mammary gland. Moreover, suckling increases SOCS mRNA in the ovary but not in the mammary
gland of pup-deprived rats. Deprivation of PRL and pups for 48 h allows the mammary gland to induce SOCS genes in
response to PRL administration, and this is associated with a decrease in basal SOCS-3 mRNA and protein expression
to the level seen in other tissues, suggesting that SOCS-3 induced refractoriness related to filling of the gland. In
reporter assays, SOCS-1, SOCS-3, and CIS, but not SOCS-2, are able to inhibit transactivation of the STAT
5-responsive -lactoglobulin promoter in transient transfection assays. Moreover, suckling results in loss of ovarian
and adrenal responsiveness to PRL administered 2 h after commencement of suckling, as determined by STAT 5 gel
shift assay. Immunohistochemistry was used to localize the cellular sites of SOCS-3 and CIS protein expression in the
ovary and adrenal gland. We propose that induced SOCS-1, SOCS-3, and CIS are actively involved in the cellular
inhibitory feedback response to physiological PRL surges in the corpus luteum and adrenal cortex during lactation, but
after pup withdrawal, the mammary gland is rendered unresponsive to PRL by increased levels of SOCS-3.
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