Disease relevance of SOCS2

• Consistent with this data, SOCS1 and SOCS2 but not SOCS3 suppressed the growth of ovarian and breast cancer cells [1].
• The SOCS1 and SOCS2 CpG islands were found to be hypermethylated in 23 and 14% of primary ovarian cancers, respectively, whereas only SOCS1 was methylated in breast cancers (9%) [1].
• SOCS1, SOCS2, and SOCS3 proteins were undetectable in healthy skin and highly expressed in the epidermis of psoriasis and allergic contact dermatitis, but were only weakly expressed in atopic dermatitis skin [2].
• The endothelial cell mRNA expression of SOCS2 (3.36+/-0.77 vs 1.76+/-0.29) and SOCS3 (2.77+/-0.60 vs 1.48+/-0.26) was enhanced in placental vascular disease [3].
• Unexpectedly, GH and SOCS2 have been recently shown to regulate neural development, neural stem cell differentiation and neuronal growth -- functions that might have important therapeutic implications for both repairing nervous system injuries and treating neurological disease [4].

High impact information on SOCS2

• Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent [5].
• Upon infection with an intracellular pathogen, SOCS-2-deficient mice had uncontrolled production of proinflammatory cytokines, decreased microbial proliferation, aberrant leukocyte infiltration and elevated mortality [5].
• SOCS-2 overexpression in Caco-2 cells inhibited cell proliferation and promoted differentiation [6].
• CONCLUSIONS: SOCS-2 is a GH-inducible, novel inhibitor of intestinal epithelial cell proliferation and intestinal growth [6].
• The inhibitory effect of E(2) was absent in cells lacking SOCS-2 but not in those lacking SOCS-1 and SOCS-3 [7].

Chemical compound and disease context of SOCS2

• The cisplatin-resistant gastric cancer cell sublines, SNU-601/Cis2 and /Cis10, were 49 and >530 times more resistant to cisplatin, respectively, compared with the drug-sensitive cells, SNU-601/WT [8].

Biological context of SOCS2

• Following labor the band for SOCS2 protein increased slightly in size which may indicate post-translational modification of SOCS2 [9].
• Consistent with the role of cytokines in human physiology, any SOCS2 imbalance could result in a broad range of pathologies such as cardiovascular diseases, insulin resistance, cancer, and severe infections, among others [10].
• We found a fast and strong upregulation of SOCS1 and SOCS3 but not of SOCS2 after ultraviolet B radiation [11].
• In addition, we mapped SOCS2 by yeast artificial chromosome (YAC) pool screening to YAC contig WC 12.5 on chromosome 12 with an unambiguous hit to CHLC.ATA19H12 and WI-5940, which is 461.5 cR from the top of the map [12].
• Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively [12].

Anatomical context of SOCS2

• Using reverse transcriptase (RT)-PCR and Western blot analysis we investigated the expression of SOCS1, SOCS2, and SOCS3 mRNA and protein, respectively, by human villous placenta, amnion and choriodecidua (n = 3-4) [9].
• Cells transfected with eight of these tagged constructs expressed the fluorescent proteins in both the nucleus and cytosol; the tagged SOCS2 was localized mostly in the latter compartment [13].
• The intravenous hGH did not induce SOCS2 mRNA expression in the hypothalamus [14].
• In addition, several studies indicate that SOCS2 also has important actions in the central nervous system, the regulation of metabolism, the immune response, the mammary gland development, cancer, and other cytokine-dependent signaling pathways [10].
• Glutathione S-transferase-hSOCS-2 associated with activated IGF-IR in lysates of mouse fibroblasts overexpressing IGF-IR [15].

Associations of SOCS2 with chemical compounds

• This paper provides evidence for regulatory interaction between a sex steroid and the GHJAKSTAT pathway, in which SOCS-2 plays a central mechanistic role [7].
• In conclusion, estrogen inhibits GH signaling, an action mediated by SOCS-2 [7].
• Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with hSOCS-2 protein. hSOCS-1 protein also interacted strongly with IGF-IR in the two-hybrid assay [15].
• Adenovirus-mediated expression of the SOCS2 gene in MIN6 cells or isolated rat islets significantly suppressed glucose-stimulated insulin secretion [16].
• We conclude that SOCS2 normally limits basal and IGF-I- and EGF-induced intestinal growth in vivo and has novel inhibitory effects on the IGF-IR tyrosine kinase pathway in intestinal epithelial cells [17].

Physical interactions of SOCS2

• Here, we show that CIS (cytokine-inducible SH2 protein) and SOCS2 can also interact with the leptin receptor [18].
• However, 55PIK and SOCS-2 also interact with the IR in the yeast two hybrid system [19].

Regulatory relationships of SOCS2

• In a yeast two-hybrid screen of a human fetal brain library, we have previously identified SOCS-2 as a binding partner of the activated IGF-I receptor (IGFIR) [20].

Other interactions of SOCS2

• Interferon (IFN)-gamma treatment induces the expression of SOCS1, SOCS2, and SOCS3 mRNAs [21].
• Specific studies targeting the SOCS genes in vivo have unveiled SOCS2 as the main regulator of somatic growth through regulation of GH/IGF-1 signaling [10].
• SOCS1, SOCS2, RASSF1a, CDKN2a, and MGMT were methylated in 75, 43, 64, 75, and 64% of melanoma samples, respectively [22].
• Jurkat cells expressed more SOCS-2 when exposed to PRL [23].
• RESULTS: SOCS-2 protein was expressed in 34 of 50 breast carcinoma samples and was positively associated with low grade, low nuclear grade, and p27 protein [24].

Analytical, diagnostic and therapeutic context of SOCS2

• The hSOCS-2 protein interacted strongly with the activated IGF-IR and not with a kinase negative mutant receptor in the two-hybrid assay [15].
• Quantitative RT-PCR revealed that SOCS2 mRNA levels were increased in the progenitor cells treated with rhEPO [25].
• ESRD patients were studied before (pre-HD) and during HD. mRNA levels of cytokines, heme oxygenase-1 (HO-1), and suppressors of cytokine signaling-2 (SOCS-2) were quantitated in the skeletal muscle by real-time polymerase chain reaction (PCR) [26].

References