KEGG   PATHWAY: puc04935
Entry
puc04935                    Pathway                                
Name
Growth hormone synthesis, secretion and action - Panthera uncia (snow leopard)
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
puc04935  Growth hormone synthesis, secretion and action
puc04935

Organism
Panthera uncia (snow leopard) [GN:puc]
Gene
125936373  somatoliberin [KO:K05260]
125917649  growth hormone-releasing hormone receptor-like [KO:K04584]
125917654  growth hormone-releasing hormone receptor-like [KO:K04584]
125917302  neuroendocrine secretory protein 55 [KO:K04632]
125918189  neuroendocrine secretory protein 55 [KO:K04632]
125936451  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
125930396  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
125934726  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
125937626  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
125909634  adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
125921018  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
125919005  adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
125915408  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
125924401  adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
125926198  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
125938268  LOW QUALITY PROTEIN: adenylate cyclase type 10-like [KO:K11265] [EC:4.6.1.1]
125925887  adenylate cyclase type 10 isoform X1 [KO:K11265] [EC:4.6.1.1]
125921837  somatostatin [KO:K05237]
125908785  somatostatin receptor type 1 [KO:K04217]
125927385  somatostatin receptor type 2 [KO:K04218]
125919573  somatostatin receptor type 3 [KO:K04219]
125928423  somatostatin receptor type 5 [KO:K04221]
125929389  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
125929845  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
125912291  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
125912461  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
125929088  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
125911260  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125911819  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
125919632  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125930188  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
125925743  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
125934155  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
125919439  cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
125928859  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125930855  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125938414  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
125927249  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
125920347  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
125920836  pituitary-specific positive transcription factor 1 [KO:K09363]
125909334  protein c-Fos [KO:K04379]
125927640  somatotropin [KO:K05438]
125929632  appetite-regulating hormone isoform X1 [KO:K05254]
125921878  growth hormone secretagogue receptor type 1 [KO:K04284]
125938671  melanocortin-2 receptor accessory protein 2 [KO:K25968]
125925154  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
125930520  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
125931611  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
125909840  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
125935985  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
125936809  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
125927372  protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
125927972  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
125915497  protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
125929585  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
125920161  inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
125938355  inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
125925380  voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
125920056  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
125931680  voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
125935006  growth hormone receptor isoform X1 [KO:K05080]
125931060  tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
125936595  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
125916347  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
125925730  SHC-transforming protein 1 isoform X1 [KO:K06279]
125928763  SHC-transforming protein 2 isoform X1 [KO:K17447]
125929330  SHC-transforming protein 3 [KO:K17448]
125909988  SHC-transforming protein 4 [KO:K17449]
125926370  growth factor receptor-bound protein 2 [KO:K04364]
125909520  son of sevenless homolog 2 isoform X1 [KO:K03099]
125917913  son of sevenless homolog 1 [KO:K03099]
125917917  son of sevenless homolog 1 [KO:K03099]
125937753  GTPase HRas isoform X1 [KO:K02833]
125918906  GTPase KRas isoform X1 [KO:K07827]
125912218  GTPase NRas [KO:K07828]
125930728  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125910082  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
125918032  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125918034  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125914884  mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
125928028  mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
125911435  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
125926571  signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
125926570  LOW QUALITY PROTEIN: signal transducer and activator of transcription 5A-like [KO:K11223]
125926542  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
125911117  insulin receptor substrate 1 [KO:K16172]
125933954  insulin receptor substrate 2 [KO:K07187]
125928238  insulin receptor substrate 1-like [KO:K17445]
125931893  insulin receptor substrate 4 isoform X1 [KO:K17446]
125913493  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
125935698  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125929237  phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
125921850  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125913143  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
125921289  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125915806  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125909102  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125925091  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125913121  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
125921776  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125919488  insulin-like growth factor I isoform X1 [KO:K05459]
125929037  transcription factor JunB [KO:K09028]
125927882  suppressor of cytokine signaling 1 [KO:K04694]
125919424  suppressor of cytokine signaling 2 [KO:K04695]
125926301  suppressor of cytokine signaling 3 [KO:K04696]
125927151  insulin-like growth factor-binding protein complex acid labile subunit [KO:K17256]
125930397  insulin-like growth factor-binding protein 3 [KO:K10138]
125924709  focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
125916426  breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
125914468  crk-like protein isoform X1 [KO:K04438]
125926856  adapter molecule crk isoform X1 [KO:K04438]
125935639  mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
125926929  dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
125927589  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
125926707  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
125916877  mitogen-activated protein kinase 10-like [KO:K04440] [EC:2.7.11.24]
125917114  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
125933328  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
125935352  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
125937867  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
125937868  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
125919741  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
125919935  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
puc04010  MAPK signaling pathway
puc04020  Calcium signaling pathway
puc04024  cAMP signaling pathway
puc04630  JAK-STAT signaling pathway
KO pathway
ko04935   
LinkDB

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