KEGG   PATHWAY: pleu04935
Entry
pleu04935                   Pathway                                
Name
Growth hormone synthesis, secretion and action - Peromyscus leucopus (white-footed mouse)
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
pleu04935  Growth hormone synthesis, secretion and action
pleu04935

Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114681231  Igfals; insulin-like growth factor-binding protein complex acid labile subunit isoform X1 [KO:K17256]
114681262  Sstr5; somatostatin receptor type 5 [KO:K04221]
114681520  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114681621  Sos1; son of sevenless homolog 1 [KO:K03099]
114681837  Ghrh; somatoliberin [KO:K05260]
114681943  Socs2; suppressor of cytokine signaling 2 [KO:K04695]
114682025  [KO:K04632]
114682029  [KO:K04632]
114682714  Crkl; crk-like protein [KO:K04438]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114682785  [KO:K11224]
114682786  Stat3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692]
114682811  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
114683276  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
114683299  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
114683897  Shc4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449]
114684032  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
114684102  Shc2; SHC-transforming protein 2 [KO:K17447]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114684224  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
114685127  [KO:K02833]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114686777  [KO:K17445]
114687523  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
114687642  Junb; transcription factor jun-B [KO:K09028]
114687991  [KO:K04374]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114688126  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114688160  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
114688488  [KO:K02833]
114688966  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
114689488  Shc3; SHC-transforming protein 3 [KO:K17448]
114689620  Ghrl; appetite-regulating hormone isoform X1 [KO:K05254]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114689726  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114689790  Ghrhr; growth hormone-releasing hormone receptor [KO:K04584]
114689930  Adcy10; adenylate cyclase type 10 [KO:K11265] [EC:4.6.1.1]
114690439  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114690458  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
114690464  Sstr2; somatostatin receptor type 2 [KO:K04218]
114690474  [KO:K05438]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114691010  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
114691441  Crk; adapter molecule crk isoform X1 [KO:K04438]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114691777  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114691978  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114692203  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114692579  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
114693019  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114693020  Mapk11; mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
114693118  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
114693397  [KO:K04217]
114693493  [KO:K02833]
114693559  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
114693595  Hras; GTPase HRas isoform X1 [KO:K02833]
114693961  Igfbp3; insulin-like growth factor-binding protein 3 [KO:K10138]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114694230  Sstr3; somatostatin receptor type 3 [KO:K04219]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114694299  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
114695106  Irs2; insulin receptor substrate 2 [KO:K07187]
114695335  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114695565  Socs1; suppressor of cytokine signaling 1 [KO:K04694]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114696438  Irs1; insulin receptor substrate 1 [KO:K16172]
114696553  [KO:K02833]
114696911  [KO:K04634]
114697089  Sst; somatostatin [KO:K05237]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114697296  Mrap2; melanocortin-2 receptor accessory protein 2 isoform X1 [KO:K25968]
114697329  Ghr; growth hormone receptor isoform X2 [KO:K05080]
114697457  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
114697543  Ghsr; growth hormone secretagogue receptor type 1 [KO:K04284]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114698038  Fos; proto-oncogene c-Fos [KO:K04379]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114698331  Irs4; insulin receptor substrate 4 [KO:K17446]
114698582  Nras; GTPase NRas [KO:K07828]
114699348  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
114699702  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114699988  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
114700619  Igf1; insulin-like growth factor I isoform X2 [KO:K05459]
114700762  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850]
114700827  Atf2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114701281  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
114701479  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114702950  Map3k1; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114703207  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114703850  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114704047  [KO:K04217]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114704659  Ptk2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114705035  Stat1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
114705057  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114705847  Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114706123  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114706162  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114706165  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114706924  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114707024  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
114707889  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
114707907  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
114708228  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
114708393  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114708477  Kras; GTPase KRas isoform X2 [KO:K07827]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114708967  Socs3; suppressor of cytokine signaling 3 [KO:K04696]
114709050  Pou1f1; pituitary-specific positive transcription factor 1 isoform X1 [KO:K09363]
114709099  Bcar1; breast cancer anti-estrogen resistance protein 1 isoform X1 [KO:K05726]
114709670  Mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114710385  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
114710523  [KO:K04371] [EC:2.7.11.24]
114710614  [KO:K04498] [EC:2.3.1.48]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114710969  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
119088838  [KO:K04438]
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
pleu04010  MAPK signaling pathway
pleu04020  Calcium signaling pathway
pleu04024  cAMP signaling pathway
pleu04630  JAK-STAT signaling pathway
KO pathway
ko04935   

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