KEGG   PATHWAY: bbis04935
Entry
bbis04935                   Pathway                                
Name
Growth hormone synthesis, secretion and action - Bison bison bison (American bison)
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
bbis04935  Growth hormone synthesis, secretion and action
bbis04935

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104980467  GHRH; somatoliberin [KO:K05260]
104980447  GHRHR; growth hormone-releasing hormone receptor isoform X1 [KO:K04584]
104989972  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
104989974  neuroendocrine secretory protein 55 [KO:K04632]
104980414  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105001032  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
104989034  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
104982045  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
104984593  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105001683  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
104999563  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
104991731  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
104988909  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105005305  adenylate cyclase type 10-like [KO:K11265] [EC:4.6.1.1]
104992964  ADCY10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
104998639  SST; somatostatin [KO:K05237]
104985253  SSTR1; somatostatin receptor type 1 [KO:K04217]
105000305  SSTR2; somatostatin receptor type 2 [KO:K04218]
105003416  SSTR3; somatostatin receptor type 3 [KO:K04219]
104998704  SSTR5; somatostatin receptor type 5 [KO:K04221]
104981671  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
104994506  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
104997186  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104999887  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105003252  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105003702  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105002941  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
104984118  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
104979678  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
104993012  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
104987449  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
104990331  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
104997842  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
104999800  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
104983973  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
104981243  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
104988985  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
104999297  POU1F1; pituitary-specific positive transcription factor 1 isoform X1 [KO:K09363]
105000057  FOS; proto-oncogene c-Fos [KO:K04379]
105000612  somatotropin [KO:K05438]
105004722  GHRL; appetite-regulating hormone isoform X1 [KO:K05254]
104985205  GHSR; growth hormone secretagogue receptor type 1 isoform X1 [KO:K04284]
104984750  MRAP2; melanocortin-2 receptor accessory protein 2 isoform X1 [KO:K25968]
104996774  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
104979885  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
104987189  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
104994462  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104984484  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104984486  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105000525  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
104986737  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
105000236  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
104991589  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105000232  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
104995001  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
104981877  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
104992358  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
104997112  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
104983362  GHR; growth hormone receptor isoform X1 [KO:K05080]
105003509  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
104980493  PLCG1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
104996518  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
104987424  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
104991966  SHC2; SHC-transforming protein 2 [KO:K17447]
104992086  SHC3; SHC-transforming protein 3 [KO:K17448]
104988263  SHC4; SHC-transforming protein 4 [KO:K17449]
105000345  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
104999941  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
104990277  SOS2; son of sevenless homolog 2 [KO:K03099]
105003692  HRAS; GTPase HRas [KO:K02833]
105000225  KRAS; GTPase KRas isoform X1 [KO:K07827]
104981582  NRAS; GTPase NRas [KO:K07828]
105004742  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104984678  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
104979900  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104986748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104995620  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105003595  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
104990441  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
104990787  signal transducer and activator of transcription 5A [KO:K11223]
104990788  signal transducer and activator of transcription 5B [KO:K11224]
104986454  IRS1; insulin receptor substrate 1 [KO:K16172]
104982211  IRS2; insulin receptor substrate 2 [KO:K07187]
104987149  insulin receptor substrate 1-like [KO:K17445]
104983354  IRS4; insulin receptor substrate 4 [KO:K17446]
104998445  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104992716  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104994333  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
104999978  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105001799  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104996058  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104986245  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
104995356  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104989637  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
105003597  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104995846  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
104992483  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
104998318  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
104999904  JUNB; LOW QUALITY PROTEIN: transcription factor jun-B [KO:K09028]
104988407  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
105000566  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
104980413  IGFBP3; LOW QUALITY PROTEIN: insulin-like growth factor-binding protein 3 [KO:K10138]
104984862  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
104996481  BCAR1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
104982909  CRKL; crk-like protein [KO:K04438]
105003906  CRK; adapter molecule crk [KO:K04438]
104998375  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
104990647  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
104990873  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
105000295  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
104998999  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104992939  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981526  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104981977  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104994938  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
104994939  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
bbis04010  MAPK signaling pathway
bbis04020  Calcium signaling pathway
bbis04024  cAMP signaling pathway
bbis04630  JAK-STAT signaling pathway
KO pathway
ko04935   
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