KEGG   PATHWAY: pvp04935
Entry
pvp04935                    Pathway                                
Name
Growth hormone synthesis, secretion and action - Pteropus vampyrus (large flying fox)
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
pvp04935  Growth hormone synthesis, secretion and action
pvp04935

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288555  [KO:K11265] [EC:4.6.1.1]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105288811  SHC4; SHC-transforming protein 4 [KO:K17449]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105288933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105289309  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
105289311  CRKL; crk-like protein [KO:K04438]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289628  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
105289648  POU1F1; pituitary-specific positive transcription factor 1 isoform X1 [KO:K09363]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105289863  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
105290070  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105290195  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105290926  SOCS1; suppressor of cytokine signaling 1 [KO:K04694]
105291271  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X4 [KO:K04430] [EC:2.7.12.2]
105291624  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105291866  CRK; adapter molecule crk isoform X1 [KO:K04438]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293217  [KO:K09047]
105293246  SOCS2; suppressor of cytokine signaling 2 [KO:K04695]
105293319  SSTR2; somatostatin receptor type 2 [KO:K04218]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293447  SOCS3; suppressor of cytokine signaling 3 [KO:K04696]
105293682  GHRHR; growth hormone-releasing hormone receptor [KO:K04584]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105294429  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105294748  IRS1; insulin receptor substrate 1 [KO:K16172]
105295155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105295517  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105296083  [KO:K04632]
105296379  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
105296460  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105296481  GHRH; somatoliberin [KO:K05260]
105296521  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296605  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105296936  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
105297140  [KO:K02649]
105297202  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105297298  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297761  [KO:K05438]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105298051  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105298404  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105298702  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105298936  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299031  GHRL; appetite-regulating hormone isoform X2 [KO:K05254]
105299105  GHR; growth hormone receptor [KO:K05080]
105299213  FOS; proto-oncogene c-Fos [KO:K04379]
105299360  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
105299371  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105299978  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105300159  [KO:K04456] [EC:2.7.11.1]
105300265  SHC3; SHC-transforming protein 3 [KO:K17448]
105300436  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105301304  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105301327  IRS2; insulin receptor substrate 2 isoform X1 [KO:K07187]
105301508  ADCY10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
105301581  IRS4; insulin receptor substrate 4 isoform X1 [KO:K17446]
105302278  SHC2; SHC-transforming protein 2 [KO:K17447]
105302452  [KO:K04634]
105303065  SSTR1; somatostatin receptor type 1 [KO:K04217]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105303098  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105303192  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
105303287  SSTR5; somatostatin receptor type 5 [KO:K04221]
105303317  IGFALS; insulin-like growth factor-binding protein complex acid labile subunit [KO:K17256]
105303899  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105304165  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105304363  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105305286  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105305354  BCAR1; breast cancer anti-estrogen resistance protein 1 isoform X4 [KO:K05726]
105305701  GHSR; growth hormone secretagogue receptor type 1 [KO:K04284]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306294  STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
105306335  [KO:K11223]
105306336  [KO:K11224]
105306466  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
105306658  SST; somatostatin [KO:K05237]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105306745  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105307165  JUNB; transcription factor jun-B [KO:K09028]
105307215  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105307575  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105307748  PTK2; focal adhesion kinase 1 [KO:K05725] [EC:2.7.10.2]
105308283  [KO:K04441] [EC:2.7.11.24]
105308299  [KO:K08041] [EC:4.6.1.1]
105308301  [KO:K10138]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105308818  [KO:K19662] [EC:2.7.11.13]
105308956  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
105309056  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105309462  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
105310472  [KO:K25968]
105310714  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
105311520  SSTR3; somatostatin receptor type 3 [KO:K04219]
105311774  [KO:K10138]
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
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04024  cAMP signaling pathway
pvp04630  JAK-STAT signaling pathway
KO pathway
ko04935   

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