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Growth Hormone Signaling Pathway
Last Updated: 2019-08-16
Growth hormone is the hormone primarily responsible for body growth. Growth hormone (GH) binds membrane-bound growth hormone receptor (GHR) to activate and enhance the binding of JAK2. This stimulates phosphorylation of JAK2 and GHR. JAK2 initiates GH signal transduction. This activation initiates multiple signalling pathways: STAT transcription factors, activation of kinases, and insulin receptor pathways. GH stimulates Signal Transducer and Activator of Transcription (STAT) and its binding to Sis-inducible elements of the c-fos promoter. C-fos expression has input from multiple pathways. The serum response element binds serum response factors and other complex transcription factors regulated by GH via the MEK/ERK pathway. STAT 5 is also involved in the synthesis of many GH-sensitive genes. STAT proteins are phosphorylated and then released from the GH/JAK2 complex. Once released, they become dimers and move to the nucleus to bind binding sites in GH-regulated genes. STAT proteins may also dimerize with other transcription factors to regulate transcription. GH can stimulate glucose transport in the cell through JAK2 stimulation of IRS proteins that recruit PI3K to regulate glucose transport.
Growth Hormone Signaling Pathway References
Grove JR, Price DJ, Banerjee P, Balasubramanyam A, Ahmad MF, Avruch J: Regulation of an epitope-tagged recombinant Rsk-1 S6 kinase by phorbol ester and erk/MAP kinase. Biochemistry. 1993 Aug 3;32(30):7727-38. doi: 10.1021/bi00081a018.Pubmed: 7688567
Jensen CJ, Buch MB, Krag TO, Hemmings BA, Gammeltoft S, Frodin M: 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J Biol Chem. 1999 Sep 17;274(38):27168-76. doi: 10.1074/jbc.274.38.27168.Pubmed: 10480933
Fujita N, Sato S, Tsuruo T: Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization. J Biol Chem. 2003 Dec 5;278(49):49254-60. doi: 10.1074/jbc.M306614200. Epub 2003 Sep 22.Pubmed: 14504289
Kazansky AV, Raught B, Lindsey SM, Wang YF, Rosen JM: Regulation of mammary gland factor/Stat5a during mammary gland development. Mol Endocrinol. 1995 Nov;9(11):1598-609. doi: 10.1210/mend.9.11.8584036.Pubmed: 8584036
Krejci P, Salazar L, Kashiwada TA, Chlebova K, Salasova A, Thompson LM, Bryja V, Kozubik A, Wilcox WR: Analysis of STAT1 activation by six FGFR3 mutants associated with skeletal dysplasia undermines dominant role of STAT1 in FGFR3 signaling in cartilage. PLoS One. 2008;3(12):e3961. doi: 10.1371/journal.pone.0003961. Epub 2008 Dec 17.Pubmed: 19088846
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.Pubmed: 22673903
Ripperger JA, Fritz S, Richter K, Hocke GM, Lottspeich F, Fey GH: Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. J Biol Chem. 1995 Dec 15;270(50):29998-30006. doi: 10.1074/jbc.270.50.29998.Pubmed: 8530402
Suh PG, Ryu SH, Moon KH, Suh HW, Rhee SG: Inositol phospholipid-specific phospholipase C: complete cDNA and protein sequences and sequence homology to tyrosine kinase-related oncogene products. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5419-23. doi: 10.1073/pnas.85.15.5419.Pubmed: 2840660
Lee SJ, Ryu SH, Suh PG: Promoter region of the rat phospholipase C-gamma 1 gene. Biochem Biophys Res Commun. 1993 Jul 15;194(1):294-300. doi: 10.1006/bbrc.1993.1818.Pubmed: 8392838
Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG, Alitalo K: Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1. J Biol Chem. 1994 Jul 15;269(28):18320-6.Pubmed: 7518429
Ono Y, Fujii T, Igarashi K, Kikkawa U, Ogita K, Nishizuka Y: Nucleotide sequences of cDNAs for alpha and gamma subspecies of rat brain protein kinase C. Nucleic Acids Res. 1988 Jun 10;16(11):5199-200. doi: 10.1093/nar/16.11.5199.Pubmed: 3387228
Kikkawa U, Ogita K, Ono Y, Asaoka Y, Shearman MS, Fujii T, Ase K, Sekiguchi K, Igarashi K, Nishizuka Y: The common structure and activities of four subspecies of rat brain protein kinase C family. FEBS Lett. 1987 Nov 2;223(2):212-6. doi: 10.1016/0014-5793(87)80291-0.Pubmed: 3666147
Mineo C, Ying YS, Chapline C, Jaken S, Anderson RG: Targeting of protein kinase Calpha to caveolae. J Cell Biol. 1998 May 4;141(3):601-10. doi: 10.1083/jcb.141.3.601.Pubmed: 9566962
This pathway was propagated using PathWhiz - Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0063807
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