KEGG   PATHWAY: xhe04912
Entry
xhe04912                    Pathway                                
Name
GnRH signaling pathway - Xiphophorus hellerii (green swordtail)
Description
Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus acts upon its receptor in the anterior pituitary to regulate the production and release of the gonadotropins, LH and FSH. The GnRHR is coupled to Gq/11 proteins to activate phospholipase C which transmits its signal to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG activates the intracellular protein kinase C (PKC) pathway and IP3 stimulates release of intracellular calcium. In addition to the classical Gq/11, coupling of Gs is occasionally observed in a cell-specific fashion. Signaling downstream of protein kinase C (PKC) leads to transactivation of the epidermal growth factor (EGF) receptor and activation of mitogen-activated protein kinases (MAPKs), including extracellular-signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPK. Active MAPKs translocate to the nucleus, resulting in activation of transcription factors and rapid induction of early genes.
Class
Organismal Systems; Endocrine system
Pathway map
xhe04912  GnRH signaling pathway
xhe04912

Organism
Xiphophorus hellerii (green swordtail) [GN:xhe]
Gene
116710756  progonadoliberin-2 [KO:K05252]
116713540  progonadoliberin-3 [KO:K05252]
116729735  gnrh1; progonadoliberin-1 [KO:K05252]
116729941  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
116718126  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
116718505  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116711262  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
116726292  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
116721781  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
116717194  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
116731245  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
116717093  adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116722709  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
116726440  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116726867  adenylate cyclase type 6-like isoform X1 [KO:K08046] [EC:4.6.1.1]
116718405  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116734023  adenylate cyclase type 8-like isoform X1 [KO:K08048] [EC:4.6.1.1]
116720923  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
116715629  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
116719875  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
116735712  adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
116725606  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116719583  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
116727897  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
116736298  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116720602  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
116735102  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
116729575  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116724051  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
116708893  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04635]
116725378  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04635]
116732702  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
116733614  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
116733615  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116712647  LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
116708418  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
116710459  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
116733729  itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116736269  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2-like [KO:K04959]
116718844  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
116718879  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
116718639  calml4; calmodulin-like protein 4 [KO:K02183]
116733986  calm1; calmodulin-1 [KO:K02183]
116713136  calmodulin-1 [KO:K02183]
116737319  calm3; calmodulin-3 [KO:K02183]
116709445  calmodulin-1 [KO:K02183]
116732193  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116719622  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116712658  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
116713126  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116727229  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116730414  calcium/calmodulin-dependent protein kinase type II delta chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116724199  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
116719536  prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
116735303  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
116719433  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
116735978  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116710982  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
116736851  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
116710265  voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851]
116725097  cacna1d; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
116722696  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
116708807  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
116727080  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
116715804  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
116711766  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
116735892  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
116713097  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
116727357  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
116735977  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
116726572  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
116720481  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
116734543  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
116736395  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116736857  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
116724360  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
116710497  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116727133  mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
116726166  pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
116735519  pla2g4c; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
116712094  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
116728474  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
116708652  pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
116717398  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
116710147  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116733855  cell division control protein 42 homolog [KO:K04393]
116734805  cell division control protein 42 homolog isoform X1 [KO:K04393]
116717718  cell division control protein 42 homolog [KO:K04393]
116731340  cell division control protein 42 homolog [KO:K04393]
116710286  cell division control protein 42 homolog [KO:K04393]
116726663  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
116734852  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116719884  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116712736  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116726919  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116714406  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116714445  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116723818  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116725965  transcription factor AP-1-like [KO:K04448]
116721147  jun; transcription factor AP-1 [KO:K04448]
116724071  transcription factor jun-D-like [KO:K04448]
116708546  cga; glycoprotein hormones alpha chain [KO:K08522]
116734185  protein-tyrosine kinase 2-beta-like isoform X1 [KO:K05871] [EC:2.7.10.2]
116715778  protein-tyrosine kinase 2-beta-like isoform X1 [KO:K05871] [EC:2.7.10.2]
116718543  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
116732222  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
116721687  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
116714743  proheparin-binding EGF-like growth factor [KO:K08523]
116712093  melanoma receptor tyrosine-protein kinase isoform X1 [KO:K04361] [EC:2.7.10.1]
116721778  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116735644  grb2; growth factor receptor-bound protein 2 [KO:K04364]
116719804  sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
116709344  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116734025  hras; GTPase HRas [KO:K02833]
116733761  kras; GTPase KRas isoform X1 [KO:K07827]
116735593  GTPase HRas-like [KO:K07827]
116719889  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116732473  map2k1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116726343  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116735682  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
116729383  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116722974  ETS domain-containing protein Elk-3-like [KO:K04375]
116714354  egr1; early growth response protein 1 [KO:K09203]
116728245  early growth response protein 1-like [KO:K09203]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00416  Phosphatidate
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:15350605
  Authors
Ruf F, Sealfon SC.
  Title
Genomics view of gonadotrope signaling circuits.
  Journal
Trends Endocrinol Metab 15:331-8 (2004)
DOI:10.1016/j.tem.2004.07.008
Reference
PMID:15613448
  Authors
Harrison GS, Wierman ME, Nett TM, Glode LM.
  Title
Gonadotropin-releasing hormone and its receptor in normal and malignant cells.
  Journal
Endocr Relat Cancer 11:725-48 (2004)
DOI:10.1677/erc.1.00777
Reference
PMID:15982836
  Authors
Pawson AJ, McNeilly AS.
  Title
The pituitary effects of GnRH.
  Journal
Anim Reprod Sci 88:75-94 (2005)
DOI:10.1016/j.anireprosci.2005.05.010
Reference
  Authors
DeGroot LJ, Jameson JL (ed).
  Title
Endocrinology (Fifth edition)
  Journal
Elsevier Saunders (2006)
Reference
PMID:10707049
  Authors
Naor Z, Benard O, Seger R.
  Title
Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor.
  Journal
Trends Endocrinol Metab 11:91-9 (2000)
DOI:10.1016/S1043-2760(99)00232-5
Reference
PMID:14596811
  Authors
Ruf F, Fink MY, Sealfon SC.
  Title
Structure of the GnRH receptor-stimulated signaling network: insights from genomics.
  Journal
Front Neuroendocrinol 24:181-99 (2003)
DOI:10.1016/S0091-3022(03)00027-X
Reference
PMID:12943720
  Authors
Farshori PQ, Shah BH, Arora KK, Martinez-Fuentes A, Catt KJ.
  Title
Activation and nuclear translocation of PKCdelta, Pyk2 and ERK1/2 by gonadotropin releasing hormone in HEK293 cells.
  Journal
J Steroid Biochem Mol Biol 85:337-47 (2003)
DOI:10.1016/S0960-0760(03)00226-7
Reference
PMID:15080147
  Authors
Shah BH, Catt KJ.
  Title
Matrix metalloproteinases in reproductive endocrinology.
  Journal
Trends Endocrinol Metab 15:47-9 (2004)
DOI:10.1016/j.tem.2004.01.004
Reference
PMID:12963732
  Authors
Roelle S, Grosse R, Aigner A, Krell HW, Czubayko F, Gudermann T.
  Title
Matrix metalloproteinases 2 and 9 mediate epidermal growth factor receptor transactivation by gonadotropin-releasing hormone.
  Journal
J Biol Chem 278:47307-18 (2003)
DOI:10.1074/jbc.M304377200
Reference
PMID:18708085
  Authors
Naor Z
  Title
Signaling by G-protein-coupled receptor (GPCR): studies on the GnRH receptor.
  Journal
Front Neuroendocrinol 30:10-29 (2009)
DOI:10.1016/j.yfrne.2008.07.001
Related
pathway
xhe04010  MAPK signaling pathway
xhe04020  Calcium signaling pathway
xhe04060  Cytokine-cytokine receptor interaction
xhe04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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