KEGG   PATHWAY: oml04912
Entry
oml04912                    Pathway                                
Name
GnRH signaling pathway - Oryzias melastigma (Indian medaka)
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
oml04912  GnRH signaling pathway
oml04912

Organism
Oryzias melastigma (Indian medaka) [GN:oml]
Gene
112162063  gnrh3; gonadotropin-releasing hormone 3 [KO:K05252]
112145366  gnrh2; progonadoliberin-2 [KO:K05252]
112152790  gnrhr4; gonadotropin releasing hormone receptor 4 [KO:K04280]
112139361  gonadotropin-releasing hormone II receptor isoform X1 [KO:K04280]
112160319  gonadotropin-releasing hormone II receptor [KO:K04280]
112160369  putative gonadotropin-releasing hormone II receptor [KO:K04280]
112145513  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
112158811  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
112147429  adcy1a; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
112150580  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
112143511  adcy2a; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112136286  adcy2b; adenylate cyclase type 2b [KO:K08042] [EC:4.6.1.1]
112151984  adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
112154945  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
112158993  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112159026  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112160437  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
112156739  adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
112144246  adcy8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
112158536  si:dkey-206f10.1; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
112137465  adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
112146809  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112147433  prkacbb; protein kinase, cAMP-dependent, catalytic, beta b isoform X1 [KO:K04345] [EC:2.7.11.11]
112150651  prkacba; protein kinase, cAMP-dependent, catalytic, beta a isoform X1 [KO:K04345] [EC:2.7.11.11]
112137621  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
112146515  prkacaa; protein kinase, cAMP-dependent, catalytic, alpha, genome duplicate a isoform X1 [KO:K04345] [EC:2.7.11.11]
112137117  atf4a; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112146289  atf4b; activating transcription factor 4b [KO:K04374]
112148434  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112163036  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
112143250  gna11b; guanine nucleotide-binding protein subunit alpha-11b isoform X1 [KO:K04635]
112150368  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04635]
112161697  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
112155970  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
112150483  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
112158335  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112158337  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
112144868  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112145415  itpr1b; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
112152271  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
112158759  itpr3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
112161269  calml4a; calmodulin-like protein 4a [KO:K02183]
112161496  calm2a; calmodulin 2a (phosphorylase kinase, delta) [KO:K02183]
112149305  calm3a; calmodulin 3a (phosphorylase kinase, delta) [KO:K02183]
112157736  calmodulin-1 [KO:K02183]
112146516  calm1a; calmodulin-1a [KO:K02183]
112154180  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112156501  camk2d1; calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
112156983  camk2d2; calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
112163512  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
112136361  camk2b1; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
112136908  camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X2 [KO:K04515] [EC:2.7.11.17]
118599716  camk2g2; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
112138354  calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
112137371  prkcaa; protein kinase C, alpha, a [KO:K02677] [EC:2.7.11.13]
112145928  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
112137352  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
112146120  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
112145195  prkcda; protein kinase C, delta a [KO:K06068] [EC:2.7.11.13]
112156742  cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
112159387  cacna1db; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
112144629  cacna1da; calcium channel, voltage-dependent, L type, alpha 1D subunit, a isoform X2 [KO:K04851]
112158801  cacna1fa; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04853]
112158663  cacna1fb; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
112144928  dihydropyridine-sensitive L-type skeletal muscle calcium channel subunit alpha-1 isoform X2 [KO:K04857]
112159792  dihydropyridine-sensitive L-type skeletal muscle calcium channel subunit alpha-1 [KO:K04857]
112156757  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
112151453  map3k22; mitogen-activated protein kinase kinase kinase 22 [KO:K04421] [EC:2.7.11.25]
112145989  map3k3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
112161704  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
112154201  map2k6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
112146636  dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
112158679  zgc:171775; STKc_p38 domain-containing protein [KO:K04441] [EC:2.7.11.24]
112152089  mapk12a; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
112158855  mapk14a; mitogen-activated protein kinase 14A isoform X2 [KO:K04441] [EC:2.7.11.24]
112159424  mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112139315  mapk14b; mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
112160268  mapk12b; mitogen-activated protein kinase 12b isoform X2 [KO:K04441] [EC:2.7.11.24]
112160269  mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
112154202  mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
112150852  pla2g4ab; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
112142405  pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
112152484  pld1b; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
112146779  pld1a; phospholipase D1a isoform X1 [KO:K01115] [EC:3.1.4.4]
112144970  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
112158705  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
112143725  cdc42l; cell division cycle 42, like [KO:K04393]
112144774  cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
112137131  cell division control protein 42 homolog [KO:K04393]
112159133  cell division control protein 42 homolog isoform X1 [KO:K04393]
112139281  cell division control protein 42 homolog [KO:K04393]
112153869  map2k4b; dual specificity mitogen-activated protein kinase kinase 4b isoform X1 [KO:K04430] [EC:2.7.12.2]
112146279  map2k4a; dual specificity mitogen-activated protein kinase kinase 4a isoform X1 [KO:K04430] [EC:2.7.12.2]
112157187  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
112154188  mapk8b; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112161471  mapk8a; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112163450  mapk10; mitogen-activated protein kinase 10 isoform X2 [KO:K04440] [EC:2.7.11.24]
112153234  mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
112147409  transcription factor AP-1 [KO:K04448]
112144196  june; junE proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
112150898  jun; transcription factor AP-1 [KO:K04448]
112161844  lhb; lutropin subunit beta [KO:K08521]
112150314  cga; glycoprotein hormones alpha chain [KO:K08522]
112157942  ptk2bb; protein tyrosine kinase 2 beta, b [KO:K05871] [EC:2.7.10.2]
112138372  protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
112160915  mmp2; 72 kDa type IV collagenase isoform X2 [KO:K01398] [EC:3.4.24.24]
112147164  mmp14b; matrix metalloproteinase-14b [KO:K07763] [EC:3.4.24.80]
112156455  mmp14a; matrix metalloproteinase-14a [KO:K07763] [EC:3.4.24.80]
112152992  hbegfa; heparin-binding EGF-like growth factor a [KO:K08523]
112147305  egfra; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
112151354  melanoma receptor tyrosine-protein kinase [KO:K04361] [EC:2.7.10.1]
112146681  grb2b; growth factor receptor-bound protein 2b [KO:K04364]
112148171  sos2; son of sevenless homolog 2 [KO:K03099]
112143420  son of sevenless homolog 1 [KO:K03099]
112151792  hrasa; HRas proto-oncogene, GTPase a [KO:K02833]
112152425  kras; GTPase KRas isoform X1 [KO:K07827]
112146394  zgc:55558; GTPase HRas [KO:K07827]
112159520  raf1a; raf-1 proto-oncogene, serine/threonine kinase a isoform X1 [KO:K04366] [EC:2.7.11.1]
112152131  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112136869  map2k2a; dual specificity mitogen-activated protein kinase kinase 2a [KO:K04369] [EC:2.7.12.2]
112136385  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112146278  mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112158910  elk1; ETS domain-containing protein Elk-3 [KO:K04375]
112138638  early growth response protein 1 [KO:K09203]
112153174  egr1; early growth response protein 1 [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
oml04010  MAPK signaling pathway
oml04020  Calcium signaling pathway
oml04060  Cytokine-cytokine receptor interaction
oml04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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