Phospho-Cot (S400) Polyclonal Antibody, 100µg, (ATB-P1049)

Description

Background:

This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.

Product datasheet:

References:

1. Honokiol thwarts gastric tumor growth and peritoneal dissemination by inhibiting Tpl2 in an orthotopic model. Pan HC, et al. Carcinogenesis, 2013 Nov. PMID 23828905
2. The protein kinase TPL2 is essential for ERK1/ERK2 activation and cytokine gene expression in airway epithelial cells exposed to pathogen-associated molecular patterns (PAMPs). Martel G, et al. PLoS One, 2013. PMID 23527104 Free PMC Article
3. MAP3K8 kinase regulates myeloma growth by cell-autonomous and non-autonomous mechanisms involving myeloma-associated monocytes/macrophages. Hebron E, et al. Br J Haematol, 2013 Mar. PMID 23252623 Free PMC Article
4. Interleukin-17 induces AP-1 activity and cellular transformation via upregulation of tumor progression locus 2 activity. Kim G, et al. Carcinogenesis, 2013 Feb. PMID 23125217
5. Involvement of Cot activity in the proliferation of ALCL lymphoma cells. Fernández M, et al. Biochem Biophys Res Commun, 2011 Aug 12. PMID 21741362
6. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase.
   Miyoshi J., Higashi T., Mukai H., Ohuchi T., Kakunaga T.
   Mol. Cell. Biol. 11:4088-4096(1991) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ONCOGENIC VARIANT. Tissue: Hepatoma.
7. The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation.
   Aoki M., Sugimoto T., Sumida S., Hamada F., Akiyama T., Toyoshima K.
   J. Biol. Chem. 268:22723-22732(1993) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION.
8. Expression cDNA cloning of a serine kinase transforming gene.
   Chan A.M., Chedid M., McGovern E.S., Popescu N.C., Miki T., Aaronson S.A.
   Oncogene 8:1329-1333(1993) [PubMed] [Europe PMC] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Bone.
9. Complete sequencing and characterization of 21,243 full-length human cDNAs.
   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
   , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
   Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC]

   Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Tongue.

10. SeattleSNPs variation discovery resource
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databasesCited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].