KEGG   PATHWAY: csab04935
Entry
csab04935                   Pathway                                
Name
Growth hormone synthesis, secretion and action - Chlorocebus sabaeus (green monkey)
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
csab04935  Growth hormone synthesis, secretion and action
csab04935

Organism
Chlorocebus sabaeus (green monkey) [GN:csab]
Gene
103214788  IRS2; insulin receptor substrate 2 [KO:K07187]
103214981  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103215199  GHR; growth hormone receptor [KO:K05080]
103215844  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103217363  ATF2; activating transcription factor 2 [KO:K04450]
103217529  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
103217717  CREB1; cAMP responsive element binding protein 1 [KO:K05870]
103217981  IRS1; insulin receptor substrate 1 [KO:K16172]
103218385  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
103218763  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103218776  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103219209  CREB3; cAMP responsive element binding protein 3 [KO:K09048]
103219496  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
103219549  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
103219624  GNAQ; G protein subunit alpha q [KO:K04634]
103219725  SHC3; SHC adaptor protein 3 [KO:K17448]
103220440  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103220665  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103221212  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103221247  GHSR; growth hormone secretagogue receptor [KO:K04284]
103221530  [KO:K11265] [EC:4.6.1.1]
103221595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103221596  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103221654  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103221701  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103221718  ATF6B; activating transcription factor 6 beta [KO:K09049]
103222594  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103222941  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103222955  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
103223271  SSTR3; somatostatin receptor 3 [KO:K04219]
103223345  ATF4; activating transcription factor 4 [KO:K04374]
103223371  EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
103223551  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103223553  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103223899  SHC1; SHC adaptor protein 1 [KO:K06279]
103223942  CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
103224167  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103224284  GNAI3; G protein subunit alpha i3 [KO:K04630]
103224540  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103224900  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103225615  MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
103225637  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103225759  SSTR5; somatostatin receptor 5 [KO:K04221]
103226113  IGFBP3; insulin like growth factor binding protein 3 [KO:K10138]
103226115  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103226267  GHRHR; growth hormone releasing hormone receptor [KO:K04584]
103226299  CREB5; cAMP responsive element binding protein 5 [KO:K09047]
103226344  IGFALS; insulin like growth factor binding protein acid labile subunit [KO:K17256]
103226652  GNAI1; G protein subunit alpha i1 [KO:K04630]
103226974  CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
103227576  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103227664  GNAI2; G protein subunit alpha i2 [KO:K04630]
103227762  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
103227941  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103228031  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103228169  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103228213  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103228298  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
103228543  POU1F1; POU class 1 homeobox 1 [KO:K09363]
103228726  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103228857  SSTR1; somatostatin receptor 1 [KO:K04217]
103228953  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103229352  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
103229784  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103229829  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103230339  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103230532  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103230649  ADCY10; adenylate cyclase 10, soluble [KO:K11265] [EC:4.6.1.1]
103230869  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103231770  CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
103231971  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103232472  IRS4; insulin receptor substrate 4 [KO:K17446]
103232667  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103233299  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103233309  BCAR1; BCAR1, Cas family scaffolding protein [KO:K05726]
103233371  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103233559  SHC2; SHC adaptor protein 2 [KO:K17447]
103233670  GNA11; G protein subunit alpha 11 [KO:K04635]
103233716  CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
103233717  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103233990  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K09028]
103234377  [KO:K04345] [EC:2.7.11.11]
103234391  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103234702  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103235232  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103235918  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103236571  CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
103237447  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103237724  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
103238242  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103238870  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
103238957  IGF1; insulin like growth factor 1 [KO:K05459]
103240024  MRAP2; melanocortin 2 receptor accessory protein 2 [KO:K25968]
103241599  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103241883  SST; somatostatin [KO:K05237]
103242119  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
103242403  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
103242535  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103243048  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103243106  SSTR2; somatostatin receptor 2 [KO:K04218]
103243132  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103243171  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103243211  [KO:K05438]
103243213  [KO:K05438]
103243214  [KO:K05438]
103243410  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
103243412  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
103243413  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
103243499  [KO:K04632]
103243509  GNAS; GNAS complex locus [KO:K04632]
103243658  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
103243843  [KO:K05438]
103245120  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103245451  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103245659  SHC4; SHC adaptor protein 4 [KO:K17449]
103245842  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103245987  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103246363  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103246408  GHRH; growth hormone releasing hormone [KO:K05260]
103246591  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103246657  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
108449889  [KO:K05438]
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
csab04010  MAPK signaling pathway
csab04020  Calcium signaling pathway
csab04024  cAMP signaling pathway
csab04630  JAK-STAT signaling pathway
KO pathway
ko04935   

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