KEGG   PATHWAY: esp04912
Entry
esp04912                    Pathway                                
Name
GnRH signaling pathway - Etheostoma spectabile (orangethroat darter)
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
esp04912  GnRH signaling pathway
esp04912

Organism
Etheostoma spectabile (orangethroat darter) [GN:esp]
Gene
116705426  progonadoliberin-3 [KO:K05252]
116687915  progonadoliberin-2 [KO:K05252]
116691498  putative gonadotropin-releasing hormone II receptor [KO:K04280]
116692724  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116694472  putative gonadotropin-releasing hormone II receptor isoform X1 [KO:K04280]
116701930  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116693014  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
116688614  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
116699106  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
116695549  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
116690645  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
116701410  adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
116699442  LOW QUALITY PROTEIN: adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
116706561  adenylate cyclase type 3-like isoform X1 [KO:K08043] [EC:4.6.1.1]
116686433  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
116698375  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
116684799  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
116692318  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
116692820  adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
116693865  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
116698871  adcy8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
116705853  adenylate cyclase type 8-like isoform X1 [KO:K08048] [EC:4.6.1.1]
116706628  adenylate cyclase type 9-like isoform X1 [KO:K08049] [EC:4.6.1.1]
116702848  adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
116698669  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116695686  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116703683  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
116700966  atf4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116704803  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04634]
116689828  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116670588  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04635]
116695435  guanine nucleotide-binding protein G(q) subunit alpha-like isoform X1 [KO:K04635]
116705016  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
116706249  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
116706250  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
116686556  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
116670665  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116687305  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
116687772  inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
116694480  itpr2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116705744  calm2; calmodulin-2 [KO:K02183]
116678688  calm3; calmodulin-3 [KO:K02183]
116706189  calm1; calmodulin-1 [KO:K02183]
116670661  calmodulin-1 [KO:K02183]
116687887  calml6; calmodulin-like protein 6 isoform X1 [KO:K02183]
116688267  calml4; calmodulin-like protein 4 [KO:K02183]
116705273  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116686178  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116669783  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
116686615  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
116671728  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116688857  calcium/calmodulin-dependent protein kinase type II subunit beta-like isoform X1 [KO:K04515] [EC:2.7.11.17]
116670566  prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116702478  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
116705456  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116703070  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116688371  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
116688666  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
116672836  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
116692928  voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851]
116687621  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04851]
116692878  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
116692230  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
116673862  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
116703027  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
116672482  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
116704886  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
116671244  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
116702724  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
116691890  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
116692206  mitogen-activated protein kinase 14A-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116693198  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
116693572  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
116687835  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
116673128  mitogen-activated protein kinase 11-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116673224  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
116671107  mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
116705632  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
116694957  pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
116703408  pla2g4c; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
116700598  phospholipase D2-like [KO:K01115] [EC:3.1.4.4]
116670513  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
116672503  LOW QUALITY PROTEIN: phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
116692732  LOW QUALITY PROTEIN: proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:2.7.10.2]
116687594  proto-oncogene tyrosine-protein kinase Src-like isoform X1 [KO:K05704] [EC:2.7.10.2]
116691327  cell division control protein 42 homolog [KO:K04393]
116692170  cell division control protein 42 homolog isoform X1 [KO:K04393]
116701833  cell division control protein 42 homolog [KO:K04393]
116688288  cell division control protein 42 homolog isoform X1 [KO:K04393]
116705506  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04430] [EC:2.7.12.2]
116671100  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
116703458  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116705548  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116697416  mitogen-activated protein kinase 9-like [KO:K04440] [EC:2.7.11.24]
116705432  mitogen-activated protein kinase 8-like isoform X1 [KO:K04440] [EC:2.7.11.24]
116671539  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116703876  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116677748  transcription factor AP-1-like [KO:K04448]
116698745  transcription factor AP-1-like [KO:K04448]
116695201  transcription factor AP-1-like [KO:K04448]
116704060  transcription factor AP-1-like [KO:K04448]
116705560  gonadotropin subunit beta-2-like [KO:K08521]
116670087  cga; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
116673744  LOW QUALITY PROTEIN: protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
116706211  ptk2b; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
116689294  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
116699164  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
116684895  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
116707003  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
116696593  proheparin-binding EGF-like growth factor [KO:K08523]
116698815  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116702397  grb2; growth factor receptor-bound protein 2 [KO:K04364]
116678819  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
116669702  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116694245  hras; GTPase HRas [KO:K02833]
116694484  kras; GTPase KRas isoform X1 [KO:K07827]
116703772  GTPase HRas-like [KO:K07827]
116693071  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116694773  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116699426  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116699428  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116695172  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116690322  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116703753  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
116679543  ETS domain-containing protein Elk-1-like [KO:K04375]
116697413  egr1; early growth response protein 1 [KO:K09203]
116700314  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
esp04010  MAPK signaling pathway
esp04020  Calcium signaling pathway
esp04060  Cytokine-cytokine receptor interaction
esp04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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