KEGG   PATHWAY: sbq04935
Entry
sbq04935                    Pathway                                
Name
Growth hormone synthesis, secretion and action - Saimiri boliviensis boliviensis (Bolivian squirrel 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
sbq04935  Growth hormone synthesis, secretion and action
sbq04935

Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101050372  GHRH; somatoliberin [KO:K05260]
101035706  GHRHR; growth hormone-releasing hormone receptor isoform X1 [KO:K04584]
101043452  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
104652116  neuroendocrine secretory protein 55 [KO:K04632]
101027981  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
101043334  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101040601  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101044688  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
101049747  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101037803  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101032672  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101034552  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
101052034  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
101048632  ADCY10; adenylate cyclase type 10 isoform X1 [KO:K11265] [EC:4.6.1.1]
101033993  SST; somatostatin [KO:K05237]
101041805  SSTR1; somatostatin receptor type 1 [KO:K04217]
104649840  SSTR2; somatostatin receptor type 2 [KO:K04218]
101029801  SSTR3; somatostatin receptor type 3 [KO:K04219]
101029032  SSTR5; somatostatin receptor type 5 [KO:K04221]
101042629  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101041681  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101032105  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101034152  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
101036705  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
101043989  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
101047300  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101034085  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
101035834  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
101034435  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101042795  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
101044974  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
101036473  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101052885  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
101041199  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X4 [KO:K09048]
101054090  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
101047355  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
101033803  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
101050224  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
101050973  POU1F1; pituitary-specific positive transcription factor 1 isoform X2 [KO:K09363]
101046701  FOS; proto-oncogene c-Fos [KO:K04379]
104649998  uncharacterized protein LOC104649998 [KO:K05438]
104649999  somatotropin-like [KO:K05438]
101053411  somatotropin-like [KO:K05438]
101053718  somatotropin-like [KO:K05438]
101039453  somatotropin-like isoform X1 [KO:K05438]
101041089  somatotropin-like [KO:K05438]
101053083  somatotropin-like [KO:K05438]
101033994  GHRL; appetite-regulating hormone isoform X1 [KO:K05254]
101029971  GHSR; growth hormone secretagogue receptor type 1 [KO:K04284]
101036156  MRAP2; melanocortin-2 receptor accessory protein 2 [KO:K25968]
101051855  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101032578  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101046851  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101047168  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
101052271  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101029401  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101046010  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101039384  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101032613  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101029556  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
101049881  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
101048916  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
101042219  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101040048  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101043152  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
101034685  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
101042350  GHR; growth hormone receptor [KO:K05080]
101046976  PLCG1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101030999  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101038895  SHC1; SHC-transforming protein 1 [KO:K06279]
101047748  SHC-transforming protein 1 [KO:K06279]
101048523  SHC2; SHC-transforming protein 2 [KO:K17447]
101028764  SHC3; SHC-transforming protein 3 [KO:K17448]
101032627  SHC4; SHC-transforming protein 4 [KO:K17449]
101038666  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101036943  SOS1; son of sevenless homolog 1 [KO:K03099]
101046427  SOS2; son of sevenless homolog 2 [KO:K03099]
101047663  HRAS; GTPase HRas isoform X2 [KO:K02833]
101047035  KRAS; GTPase KRas isoform X1 [KO:K07827]
101036877  NRAS; GTPase NRas [KO:K07828]
101054052  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101040361  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101036151  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101030811  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101049662  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
101049987  signal transducer and activator of transcription 5A [KO:K11223]
101043203  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
101035868  IRS1; insulin receptor substrate 1 [KO:K16172]
101038649  IRS2; insulin receptor substrate 2 [KO:K07187]
101035392  IRS4; insulin receptor substrate 4 [KO:K17446]
101032496  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101033359  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101050592  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101029768  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101052779  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101027982  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101034861  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101045714  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101040766  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101047083  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101051107  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
101036963  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
101048399  JUNB; transcription factor jun-B [KO:K09028]
101050866  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
101040467  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
101046533  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
101048750  IGFALS; insulin-like growth factor-binding protein complex acid labile subunit [KO:K17256]
101052217  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
101041293  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
101051048  CRKL; crk-like protein [KO:K04438]
101029260  CRK; adapter molecule crk [KO:K04438]
101054366  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
101034633  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
101037589  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
101030219  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101039160  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101027742  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
101048066  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101037444  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101044137  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101040899  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101052690  MAPK11; mitogen-activated protein kinase 11 [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
sbq04010  MAPK signaling pathway
sbq04020  Calcium signaling pathway
sbq04024  cAMP signaling pathway
sbq04630  JAK-STAT signaling pathway
KO pathway
ko04935   
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