KEGG   PATHWAY: cbai04935
Entry
cbai04935                   Pathway                                
Name
Growth hormone synthesis, secretion and action - Camelus bactrianus (Bactrian camel)
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
cbai04935  Growth hormone synthesis, secretion and action
cbai04935

Organism
Camelus bactrianus (Bactrian camel) [GN:cbai]
Gene
105073495  GHRH; somatoliberin [KO:K05260]
105081866  GHRHR; growth hormone-releasing hormone receptor [KO:K04584]
105071802  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
105071803  neuroendocrine secretory protein 55 [KO:K04632]
105080525  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
105081234  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105063873  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
105068818  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105081635  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105076187  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
105074271  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105082946  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105064797  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105083904  adenylate cyclase type 10-like [KO:K11265] [EC:4.6.1.1]
105068061  ADCY10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
105072342  SST; somatostatin [KO:K05237]
105078473  SSTR1; somatostatin receptor type 1 [KO:K04217]
105065700  SSTR2; somatostatin receptor type 2 [KO:K04218]
105073154  SSTR3; somatostatin receptor type 3 [KO:K04219]
105062396  SSTR5; somatostatin receptor type 5 [KO:K04221]
105080234  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105062385  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105063651  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105075498  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105068302  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105072963  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105073454  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105073101  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105076770  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105078379  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105068196  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
105063046  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105067333  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105082021  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105074031  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
105064798  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105073084  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105077951  POU1F1; pituitary-specific positive transcription factor 1 isoform X1 [KO:K09363]
105075289  FOS; proto-oncogene c-Fos [KO:K04379]
105069779  somatotropin [KO:K05438]
105067457  GHRL; appetite-regulating hormone isoform X1 [KO:K05254]
105063298  GHSR; LOW QUALITY PROTEIN: growth hormone secretagogue receptor type 1 [KO:K04284]
105083111  MRAP2; melanocortin-2 receptor accessory protein 2 [KO:K25968]
105067298  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105078179  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105077045  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105082996  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105082997  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
105070632  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105063941  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
105073669  PRKCB; LOW QUALITY PROTEIN: protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
105074322  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105074761  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105062304  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
105064212  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105070011  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
105076642  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
105079596  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105079415  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105070877  GHR; growth hormone receptor [KO:K05080]
105079173  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
105071939  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105078942  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
105068173  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105078342  SHC2; SHC-transforming protein 2 [KO:K17447]
105065419  SHC3; SHC-transforming protein 3 [KO:K17448]
105077007  SHC4; SHC-transforming protein 4 [KO:K17449]
105065653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105078489  SOS2; son of sevenless homolog 2 [KO:K03099]
105078987  SOS1; son of sevenless homolog 1 [KO:K03099]
105069943  HRAS; GTPase HRas isoform X1 [KO:K02833]
105062297  KRAS; GTPase KRas [KO:K07827]
105079555  NRAS; GTPase NRas [KO:K07828]
105067475  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105069422  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105078209  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105082839  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105069349  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105063982  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
105080116  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
105080117  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
105080118  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
105064075  IRS1; insulin receptor substrate 1 [KO:K16172]
105078567  uncharacterized protein LOC105078567 [KO:K17445]
105061987  IRS4; insulin receptor substrate 4 [KO:K17446]
105082679  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105064416  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
105065663  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105063312  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105071167  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105066839  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105079975  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105083596  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105062855  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105070974  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105081598  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105075052  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
105068335  JUNB; transcription factor jun-B [KO:K09028]
105074255  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
105074996  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
105065593  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105064871  IGFALS; insulin-like growth factor-binding protein complex acid labile subunit [KO:K17256]
105074777  focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105078652  BCAR1; LOW QUALITY PROTEIN: breast cancer anti-estrogen resistance protein 1 [KO:K05726]
105070566  CRKL; crk-like protein [KO:K04438]
105071519  CRK; adapter molecule crk [KO:K04438]
105077858  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
105084150  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105077599  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
105063918  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
105075609  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105077723  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105062001  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105064175  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105064176  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105070806  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105070807  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
cbai04010  MAPK signaling pathway
cbai04020  Calcium signaling pathway
cbai04024  cAMP signaling pathway
cbai04630  JAK-STAT signaling pathway
KO pathway
ko04935   
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