KEGG   PATHWAY: btax04935
Entry
btax04935                   Pathway                                
Name
Growth hormone synthesis, secretion and action - Budorcas taxicolor (takin)
Description
Growth hormone (GH) is a peptide hormone secreted from the anterior pituitary and plays a critical role in cell growth, development, and metabolism throughout the body. GH secretion occurs episodically and is primarily under the control of two hypothalamic neuroendocrine hormones: GH-releasing hormone (GHRH), which stimulates GH secretion, and somatostatin, which inhibits GH secretion. GHRH interacts with a G protein-coupled receptor (GHRHR) in somatotroph cells to activate the cAMP signaling pathway, which leads to increased GH mRNA transcription and release. Once released into the circulation, GH binds to cell-surface GHR in target tissues such as liver, muscle, bone, and adipose tissue. Binding leads to activation of JAK2 that in turn triggers an array of signaling cascade including Raf-MEK-ERK, PI3K-Akt, and STAT5. ERK, Akt, and STAT5 all promote growth via the synthesis and secretion of IGF-1.
Class
Organismal Systems; Endocrine system
Pathway map
btax04935  Growth hormone synthesis, secretion and action
btax04935

Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128058848  GHRH; somatoliberin [KO:K05260]
128046820  GHRHR; growth hormone-releasing hormone receptor [KO:K04584]
128058250  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
128058829  neuroendocrine secretory protein 55 [KO:K04632]
128046764  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
128066123  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
128056879  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
128053854  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
128067499  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
128047362  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
128063240  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
128059256  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
128043555  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
128056822  adenylate cyclase type 10-like [KO:K11265] [EC:4.6.1.1]
128045268  ADCY10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
128056109  SST; somatostatin [KO:K05237]
128066943  SSTR1; somatostatin receptor type 1 [KO:K04217]
128065401  SSTR2; somatostatin receptor type 2 [KO:K04218]
128048753  SSTR3; somatostatin receptor type 3 [KO:K04219]
128043489  SSTR5; somatostatin receptor type 5 [KO:K04221]
128044413  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
128057155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
128046449  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
128050339  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
128044465  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
128071103  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
128061475  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
128065610  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
128047885  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
128048350  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
128044759  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
128051508  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
128052214  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
128046532  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
128060385  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
128046584  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
128056429  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
128043638  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
128047516  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
128055395  POU1F1; pituitary-specific positive transcription factor 1 [KO:K09363]
128053951  FOS; protein c-Fos [KO:K04379]
128065055  GH1; somatotropin [KO:K05438]
128054531  GHRL; appetite-regulating hormone [KO:K05254]
128056061  GHSR; growth hormone secretagogue receptor type 1 [KO:K04284]
128053506  MRAP2; melanocortin-2 receptor accessory protein 2 [KO:K25968]
128052307  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
128050674  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
128058011  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
128058303  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
128054050  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
128068545  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
128065393  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128066420  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
128063096  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
128046429  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
128048527  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
128056281  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
128061188  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
128048945  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
128052044  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
128070004  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
128065987  GHR; growth hormone receptor isoform X1 [KO:K05080]
128052316  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
128058189  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
128063111  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
128044445  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
128051196  SHC2; SHC-transforming protein 2 [KO:K17447]
128052614  SHC3; SHC-transforming protein 3 [KO:K17448]
128054009  SHC4; SHC-transforming protein 4 [KO:K17449]
128064562  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
128053892  SOS2; son of sevenless homolog 2 [KO:K03099]
128055374  SOS1; son of sevenless homolog 1 [KO:K03099]
128068689  HRAS; GTPase HRas isoform X1 [KO:K02833]
128047937  KRAS; GTPase KRas [KO:K07827]
128044537  NRAS; GTPase NRas [KO:K07828]
128043403  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128050664  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128071221  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
128065049  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
128065012  signal transducer and activator of transcription 5A [KO:K11223]
128064838  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
128069000  IRS1; insulin receptor substrate 1 [KO:K16172]
128057660  IRS2; LOW QUALITY PROTEIN: insulin receptor substrate 2 [KO:K07187]
128043668  insulin receptor substrate 1-like [KO:K17445]
128070573  IRS4; insulin receptor substrate 4 [KO:K17446]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128063870  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128067048  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061491  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
128061687  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
128043889  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
128048032  IGF1; insulin-like growth factor I [KO:K05459]
128050788  JUNB; transcription factor JunB [KO:K09028]
128043765  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
128047912  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
128064715  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
128060152  IGFALS; insulin-like growth factor-binding protein complex acid labile subunit [KO:K17256]
128046632  IGFBP3; insulin-like growth factor-binding protein 3 [KO:K10138]
128059235  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
128062963  BCAR1; LOW QUALITY PROTEIN: breast cancer anti-estrogen resistance protein 1 [KO:K05726]
128064843  CRK; adapter molecule crk isoform X1 [KO:K04438]
128062501  CRKL; crk-like protein [KO:K04438]
128065982  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
128064641  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
128064467  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
128065178  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
128051495  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
128047244  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
128049619  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
128047426  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
128048391  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
128055294  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
128055801  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
  Authors
Nishad R, Mukhi D, Menon R K, Pasupulati A.
  Title
Growth Hormone and Metabolic Homeostasis
  Journal
Eur Med J 6:78-87 (2018)
Reference
PMID:30775002
  Authors
Lu M, Flanagan JU, Langley RJ, Hay MP, Perry JK
  Title
Targeting growth hormone function: strategies and therapeutic applications.
  Journal
Signal Transduct Target Ther 4:3 (2019)
DOI:10.1038/s41392-019-0036-y
Reference
PMID:8874495
  Authors
Argetsinger LS, Carter-Su C
  Title
Mechanism of signaling by growth hormone receptor.
  Journal
Physiol Rev 76:1089-107 (1996)
DOI:10.1152/physrev.1996.76.4.1089
Reference
PMID:8815791
  Authors
Carter-Su C, Schwartz J, Smit LS
  Title
Molecular mechanism of growth hormone action.
  Journal
Annu Rev Physiol 58:187-207 (1996)
DOI:10.1146/annurev.ph.58.030196.001155
Reference
PMID:10912517
  Authors
Carter-Su C, Rui L, Herrington J
  Title
Role of the tyrosine kinase JAK2 in signal transduction by growth hormone.
  Journal
Pediatr Nephrol 14:550-7 (2000)
DOI:10.1007/s004670000366
Reference
PMID:29487568
  Authors
Dehkhoda F, Lee CMM, Medina J, Brooks AJ
  Title
The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects.
  Journal
Front Endocrinol (Lausanne) 9:35 (2018)
DOI:10.3389/fendo.2018.00035
Reference
PMID:26421979
  Authors
Carter-Su C, Schwartz J, Argetsinger LS
  Title
Growth hormone signaling pathways.
  Journal
Growth Horm IGF Res 28:11-5 (2016)
DOI:10.1016/j.ghir.2015.09.002
Reference
PMID:28435436
  Authors
Berryman DE, Henry B, Hjortebjerg R, List EO, Kopchick JJ
  Title
Developments in our understanding of the effects of growth hormone on white adipose tissue from mice: implications to the clinic.
  Journal
Expert Rev Endocrinol Metab 11:197-207 (2016)
DOI:10.1586/17446651.2016.1147950
Reference
PMID:9837978
  Authors
Zhu T, Goh EL, LeRoith D, Lobie PE
  Title
Growth hormone stimulates the formation of a multiprotein signaling complex involving p130(Cas) and CrkII. Resultant activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK).
  Journal
J Biol Chem 273:33864-75 (1998)
DOI:10.1074/jbc.273.50.33864
Reference
  Authors
Choi S (ed).
  Title
Encyclopedia of Signaling Molecules
  Journal
Springer International Publishing
DOI:10.1007/978-1-4614-6438-9_101674-1
Reference
PMID:11997217
  Authors
Gracia-Navarro F, Castano JP, Malagon MM, Sanchez-Hormigo A, Luque RM, Hickey GJ, Peinado JR, Delgado E, Martinez-Fuentes AJ
  Title
Research progress in the stimulatory inputs regulating growth hormone (GH) secretion.
  Journal
Comp Biochem Physiol B Biochem Mol Biol 132:141-50 (2002)
DOI:10.1016/s1096-4959(01)00544-9
Reference
PMID:9167959
  Authors
Bertherat J
  Title
Nuclear effects of the cAMP pathway activation in somatotrophs.
  Journal
Horm Res 47:245-50 (1997)
DOI:10.1159/000185471
Reference
PMID:8625613
  Authors
Tuggle CK, Trenkle A
  Title
Control of growth hormone synthesis.
  Journal
Domest Anim Endocrinol 13:1-33 (1996)
DOI:10.1016/0739-7240(95)00059-3
Reference
PMID:10525051
  Authors
Cohen LE, Hashimoto Y, Zanger K, Wondisford F, Radovick S
  Title
CREB-independent regulation by CBP is a novel mechanism of human growth hormone gene expression.
  Journal
J Clin Invest 104:1123-30 (1999)
DOI:10.1172/JCI7308
Reference
PMID:25302229
  Authors
Khatib N, Gaidhane S, Gaidhane AM, Khatib M, Simkhada P, Gode D, Zahiruddin QS
  Title
Ghrelin: ghrelin as a regulatory Peptide in growth hormone secretion.
  Journal
J Clin Diagn Res 8:MC13-7 (2014)
DOI:10.7860/JCDR/2014/9863.4767
Reference
PMID:16628271
  Authors
Lengyel AM
  Title
From growth hormone-releasing peptides to ghrelin: discovery of new modulators of GH secretion.
  Journal
Arq Bras Endocrinol Metabol 50:17-24 (2006)
DOI:10.1590/s0004-27302006000100004
Reference
PMID:15927771
  Authors
Anderson LL, Jeftinija S, Scanes CG, Stromer MH, Lee JS, Jeftinija K, Glavaski-Joksimovic A
  Title
Physiology of ghrelin and related peptides.
  Journal
Domest Anim Endocrinol 29:111-44 (2005)
DOI:10.1016/j.domaniend.2005.02.033
Reference
PMID:14610293
  Authors
Camina JP, Carreira MC, Micic D, Pombo M, Kelestimur F, Dieguez C, Casanueva FF
  Title
Regulation of ghrelin secretion and action.
  Journal
Endocrine 22:5-12 (2003)
DOI:10.1385/ENDO:22:1:5
Reference
PMID:22243899
  Authors
Yang SK, Steyn F, Chen C
  Title
Influence of membrane ion channel in pituitary somatotrophs by hypothalamic regulators.
  Journal
Cell Calcium 51:231-9 (2012)
DOI:10.1016/j.ceca.2011.12.005
Reference
PMID:19884662
  Authors
Melmed S
  Title
Acromegaly pathogenesis and treatment.
  Journal
J Clin Invest 119:3189-202 (2009)
DOI:10.1172/JCI39375
Reference
PMID:31911434
  Authors
Rouault AAJ, Rosselli-Murai LK, Hernandez CC, Gimenez LE, Tall GG, Sebag JA
  Title
The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a.
  Journal
Sci Signal 13:eaax4569 (2020)
DOI:10.1126/scisignal.aax4569
Related
pathway
btax04010  MAPK signaling pathway
btax04020  Calcium signaling pathway
btax04024  cAMP signaling pathway
btax04630  JAK-STAT signaling pathway
KO pathway
ko04935   
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