Jak/Stat Pathway Inhibitors Antibody Sampler Kit, BioAssay™

Suitable for use in Western Blot. Other applications not tested.

Jak (Janus Kinase) and Stat (signal transducer and activator of transcription) proteins are utilized by receptors for a wide varity of ligands including cytokines, hormones, growth factors, and neurotransmitters. Jaks and Stats play important roles in oncogenesis, tumor progression, angiogenesis, cell motility, immune responses, and stem cell differentiation. Therefore, regulation of Jak/Stat signaling is crucial to prevent aberrant signaling which can lead to disease progression. Two methods for regulating Jak/Stat signaling involve SOCS and PIAS proteins. The SOCS (suppressor or cytokine signaling) family members are negative regulators of cytokine signal transduction that inhibit the Jak/Stat pathway and consist of 8 known members, including the originally identified protein CIS1 (cytokine-inducible SH2-containing protein) and SOCS1-SOCS7. Each SOCS family member contains a central SH2 domain and a conserved carboxy-terminal motif designated as the SOCS box. These proteins are important regulators of cytokine signaling, proliferation, differentiation, and immune responses. SOCS proteins are involved in regulating over 30 cytokines, including interleukins, growth hormone (GH), interferons, leptin, and leukemia inhibitory factor. SOCS1, also known as JAB (Janus Kinase binding protein) and SSI-1 (Stat-induced Stat inhibitor-1), shares the most homology with SOCS3 and both are highly induced by cytokines. Both SOCS1 and SOCS3 directly inhibit Jak activity; SOCS1 inhibits Jak through an interaction involving a phospohotyrosine located in the kinase activation loop; SOCS3 inhibits Jak via its SH2 domain. In addition to inhibiting Jak/Stat signaling, the SOCS box of SOCS1 and SOCS3 can trigger ubiquitin-mediated degradation of proteins within and outside the Jak/Stat pathway. SOCS2 is also incduced upon cytokine stimulation and the activity of SOCS2 has been predominately linked to GH and insulin-like growth factor signaling by binding to tyrosine-phosphorylated receptors via its SH2 domain. The PIAS (protein inhibitor of activated Stats) proteins, which include PIAS1, PIAS3, PIASx, and PIASy (PIAS4), were originally characterized based on their interaction with the Stat family of transcription factors. PIAS1, PIAS3, and PIASx interact with and repress Stat1, Stat3, and Stat4, respectively. The PIAS family contains a conserved RING domain that has been linked to function as a SUMO (small ubiquitin-related modifer) ligase, coupling the SUMO conjugating enzyme Ubc9 with its substrate proteins leading to regulation of transcription factors through distinct mechanisms including NF-kB, c-Jun, Oct-4, p53, and SMADs. PIAS4 is a specific SUMO-E3 ligase for Ets-1 and represses Ets-1 dependent transcription in addition to altering the nuclear localization and reducing the transcriptional activity of C/EBPdelta, thereby enhancing cell proliferation and migration.

394742, SOCS1, Pab, 1x20ul 394743, SOCS2, Pab, 1x20ul 394747, SOCS3, Pab, 1x20ul 393011, PIAS1, Pab, 1x20ul 393012, PIAS3, Pab, 1x20ul Goat Anti-Rabbit IgG (H+L)(peroxidase/HRP conjugated), 1x120ul

Suitable for use in Western Blot. Other applications not tested.

Western Blot: 1:500-1:2000 Optimal dilutions to be determined by the researcher.

Human

38220000