Disease relevance of SOCS6

• Prognostic and predictive relevance of DNAM-1, SOCS6 and CADH-7 genes on chromosome 18q in colorectal cancer [1].
• In particular, an activation of STAT-4 and STAT-3 in T cells seems to play a key pathogenic role in Crohn's disease [2].
• STAT4 activation in smokers and patients with chronic obstructive pulmonary disease [3].

Psychiatry related information on SOCS6

• Somatoform autonomic dysfunction, a diagnostic category proposed by ICD-10, included fewer patients diagnosed with somatization disorder than the criteria of Escobar and colleagues for abridged somatization disorder (SSI-4/6: this Journal 177:140-146, 1989) [4].
• In-depth explorations, including problem solving and projection to the future, occurred 2.59 times in interviews alone (CI 3.62-1.56) and 0.794 times in CIRs (CI 1.12-0.46) (p <.001) [5].

High impact information on SOCS6

• The crystal structure of an NH2-terminal conserved domain (N-domain) comprising the first 123 residues of STAT-4 was determined at 1.45 angstroms [6].
• Three exons overlap with ING2 (a putative tumor suppressor) and with a homologue of CIS4 (cytokine-inducible SH2 protein 4), both of which are encoded by the opposite strand [7].
• IL12 phosphorylation of STAT4 can be observed in HUVEC that have been transduced to express the IL12R [8].
• STAT4 signaling, activated by either interleukin 12 (IL12) or interferon alpha (IFNalpha), promotes T(H)1 responses in CD4(+) T cells [8].
• Interferon alpha but not interleukin 12 activates STAT4 signaling in human vascular endothelial cells [8].

Biological context of SOCS6

• We then studied the role of signal pathways in SOCS6 stability with PMA [9].
• STAT4 requires the N-terminal domain for efficient phosphorylation [10].
• STAT4 has multiple domains that have distinct functions in signaling and gene activation [10].
• These data support a new model wherein the N-terminal domain is required to mediate the phosphorylation of STAT4 in addition to the previously documented role in gene transactivation [10].
• Our results propose participation of Jak2 and STAT4 in IL-2-induced up-regulation of c-myc [11].

Anatomical context of SOCS6

• The increased SOCS6 stability and Erk activation by PMA were both conserved in another cell line, MCF7 [9].
• Cultured human umbilical vein EC (HUVEC) express low levels of STAT4, which may be tyrosine-phosphorylated by treatment with IFNalpha but not IL12 [8].
• Th2 cells remained responsive to IL-12, which repressed STAT6 DNA binding and activated STAT4, and switched the cells to Th1 [12].
• In Th1 cells, IL-12 activated both STAT6 and STAT4, and IL-4 activated STAT6, but in both cases the Th1 phenotype remained [12].
• The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-kappaB), STAT-4 and IFN-gamma proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease [13].

Associations of SOCS6 with chemical compounds

• We confirmed that IL-2-mediated signaling involves activation by phosphorylation of Jak2 tyrosine kinase and subsequently STAT4 [11].
• They also reveal the existence of sperm specific mRNAs coding for the transcription factor Stat 4, the cyclin B1 and for the testicular isozyme of the angiotensin converting enzyme ACE [14].

Other interactions of SOCS6

• However, Th2 cells remained responsive to IL-12, which repressed STAT6 DNA binding but activated STAT4, and this coincided with a suppression of IL-4/IL-5 and an induction of IFN-gamma [12].
• Atopic T cells expressed regular levels of CD3, CD28 and Stat4, the main signal transducer and activator of transcription for IL-12 [15].
• The transcription factor STAT4 binds the TTCCAATAA motif within this responsive element and, therefore, is probably involved in enhancing c-myc transcription upon IL-2 stimulation [11].

Analytical, diagnostic and therapeutic context of SOCS6

• STAT4 (signal transducer and activator of transcription-4) mediates biological effects in response to interleukin-12 (IL-12) [10].
• The aim of the present study was to evaluate the genetic status of three novel putative tumor suppressors, Cadh-7, DNAX accessory molecule-1 (Dnam-1) and suppressor of cytokine signaling (Socs6) on chromosome 18q and to correlate molecular results with patient survival and benefit from adjuvant chemotherapy [1].

References