KEGG   PATHWAY: pov04912
Entry
pov04912                    Pathway                                
Name
GnRH signaling pathway - Paralichthys olivaceus (Japanese flounder)
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
pov04912  GnRH signaling pathway
pov04912

Organism
Paralichthys olivaceus (Japanese flounder) [GN:pov]
Gene
109642372  gnrh1; progonadoliberin-1 [KO:K05252]
109629059  gnrh2; progonadoliberin-2 [KO:K05252]
109631559  progonadoliberin-3 [KO:K05252]
109647897  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109643632  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
109631640  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109624854  putative gonadotropin-releasing hormone II receptor [KO:K04280]
109624064  gonadotropin-releasing hormone II receptor-like [KO:K04280]
109635337  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
109630898  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
109643317  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
109637504  adcy1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
109631507  adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
109632042  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
109632037  adcy3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
109637957  adenylate cyclase type 5-like isoform X1 [KO:K08045] [EC:4.6.1.1]
109630770  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
109635053  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
109625125  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109646927  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
109636103  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
109627430  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
109638721  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
109627640  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
109634223  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109625861  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109642250  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109643580  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
109639271  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
109636384  guanine nucleotide-binding protein subunit alpha-11-like isoform X1 [KO:K04634]
109626221  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109626222  guanine nucleotide-binding protein subunit alpha-14-like [KO:K04634]
109638174  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
109625670  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04635]
109634719  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
109632377  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109632378  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
109627890  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2-like [KO:K05858] [EC:3.1.4.11]
109628963  inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109628992  inositol 1,4,5-trisphosphate receptor type 1-like [KO:K04958]
109624047  itpr2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109642872  inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
109637278  calml4; calmodulin-like protein 4 [KO:K02183]
109638542  calml6; calmodulin-like protein 6 [KO:K02183]
109632728  calm2; calmodulin [KO:K02183]
109628113  calmodulin [KO:K02183]
109632493  calm1; calmodulin [KO:K02183]
109630080  calmodulin [KO:K02183]
109648074  calmodulin-like protein 4 [KO:K02183]
109633197  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109641257  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
109643417  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
109643698  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
109637646  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
109626490  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109637852  calcium/calmodulin-dependent protein kinase type II subunit delta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
109627602  prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109638270  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109639494  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
109629305  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
109632862  voltage-dependent L-type calcium channel subunit alpha-1C-like [KO:K04850]
109630732  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
109638586  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
109643812  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
109642986  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
109630550  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
109640231  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
109629552  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
109629839  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
109633995  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
109634498  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
109634317  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
109647356  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
109630822  mitogen-activated protein kinase 14A-like isoform X1 [KO:K04441] [EC:2.7.11.24]
109632714  mitogen-activated protein kinase 14-like [KO:K04441] [EC:2.7.11.24]
109632715  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
109629252  mitogen-activated protein kinase 14A [KO:K04441] [EC:2.7.11.24]
109630593  mitogen-activated protein kinase 14B-like [KO:K04441] [EC:2.7.11.24]
109630994  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
109638988  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
109641502  mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
109636707  pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
109641948  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
109644758  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
109628714  phospholipase D2-like [KO:K01115] [EC:3.1.4.4]
109635513  src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
109641595  cell division control protein 42 homolog [KO:K04393]
109643474  cell division control protein 42 homolog [KO:K04393]
109642445  cell division control protein 42 homolog isoform X1 [KO:K04393]
109629172  cell division control protein 42 homolog isoform X1 [KO:K04393]
109626687  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
109633989  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
109627519  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
109626552  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
109626878  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109633007  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
109626434  mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109625845  transcription factor AP-1-like [KO:K04448]
109643961  jun; transcription factor AP-1 [KO:K04448]
109641987  gonadotropin subunit beta-2-like [KO:K08521]
109627943  cga; glycoprotein hormones alpha chain [KO:K08522]
109637185  gonadotropin subunit beta-1-like isoform X1 [KO:K05250]
109636011  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
109640090  protein-tyrosine kinase 2-beta-like isoform X1 [KO:K05871] [EC:2.7.10.2]
109625153  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
109641241  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
109640512  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
109625710  proheparin-binding EGF-like growth factor [KO:K08523]
109646379  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
109646791  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
109645925  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
109641399  grb2; growth factor receptor-bound protein 2 [KO:K04364]
109636299  sos2; son of sevenless homolog 2 [KO:K03099]
109646414  son of sevenless homolog 1-like [KO:K03099]
109638968  hras; GTPase HRas [KO:K02833]
109641467  GTPase HRas-like [KO:K07827]
109624348  kras; GTPase KRas isoform X1 [KO:K07827]
109635227  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109624327  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
109625750  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
109639504  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
109640677  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109646087  ETS domain-containing protein Elk-3-like [KO:K04375]
109640856  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
pov04010  MAPK signaling pathway
pov04020  Calcium signaling pathway
pov04060  Cytokine-cytokine receptor interaction
pov04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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