KEGG   PATHWAY: xma04912
Entry
xma04912                    Pathway                                
Name
GnRH signaling pathway - Xiphophorus maculatus (southern platyfish)
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
xma04912  GnRH signaling pathway
xma04912

Organism
Xiphophorus maculatus (southern platyfish) [GN:xma]
Gene
102223304  progonadoliberin-3 [KO:K05252]
102227804  gnrh2; progonadoliberin-2 [KO:K05252]
102232142  gnrh1; progonadoliberin-1 [KO:K05252]
102226378  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
102216497  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
102222539  gonadotropin-releasing hormone II receptor-like [KO:K04280]
106700302  gonadotropin-releasing hormone II receptor-like isoform X2 [KO:K04280]
102220069  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
102237275  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X2 [KO:K04632]
102227141  adenylate cyclase type 1-like isoform X2 [KO:K08041] [EC:4.6.1.1]
102232616  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
102225654  adenylate cyclase type 2-like isoform X2 [KO:K08042] [EC:4.6.1.1]
102219843  adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
102219355  adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102229859  adcy5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
102235040  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
102232614  adcy6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102223009  adcy7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102236399  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
102218852  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102231024  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
102230840  adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
102231255  adenylate cyclase type 9-like [KO:K08049] [EC:4.6.1.1]
102230641  cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
102225635  prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102237217  cAMP-dependent protein kinase catalytic subunit beta-like isoform X2 [KO:K04345] [EC:2.7.11.11]
102230273  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102232234  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
102223838  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102230612  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102218075  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
102230367  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
102238377  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04635]
102217878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
102224078  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102219479  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3-like [KO:K05858] [EC:3.1.4.11]
102230660  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102223820  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102217419  inositol 1,4,5-trisphosphate receptor type 1-like isoform X1 [KO:K04958]
102227088  itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
102220160  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102237995  itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102218415  calm2; calmodulin-2 [KO:K02183]
102227246  calmodulin [KO:K02183]
102222105  calm3; calmodulin-3 [KO:K02183]
102225225  calm1; calmodulin-1 [KO:K02183]
102222024  calml4; calmodulin-like protein 4 [KO:K02183]
102233374  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X11 [KO:K04515] [EC:2.7.11.17]
102238314  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X3 [KO:K04515] [EC:2.7.11.17]
102222103  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
102218714  camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
102219759  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X6 [KO:K04515] [EC:2.7.11.17]
102220401  calcium/calmodulin-dependent protein kinase type II delta 1 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
102220084  calcium/calmodulin-dependent protein kinase type II delta chain isoform X1 [KO:K04515] [EC:2.7.11.17]
102228309  prkca; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
102227289  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
102228928  protein kinase C beta type-like isoform X1 [KO:K19662] [EC:2.7.11.13]
102235758  prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
102232189  prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102230290  cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102234425  cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102234457  voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851]
102223947  voltage-dependent L-type calcium channel subunit alpha-1D-like [KO:K04853]
102230940  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04853]
102237099  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
102232571  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
102228349  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
102234853  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
102230475  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
102219049  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
102221885  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102231047  mitogen-activated protein kinase 14A isoform X1 [KO:K04441] [EC:2.7.11.24]
102218102  mitogen-activated protein kinase 14A-like [KO:K04441] [EC:2.7.11.24]
102233918  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102223674  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
102223422  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102233752  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
102223477  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
102229633  mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102235312  pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
111611546  pla2g4c; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
102225016  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
102217553  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
102220287  pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102227098  proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102227197  proto-oncogene tyrosine-protein kinase Src isoform X4 [KO:K05704] [EC:2.7.10.2]
102236058  cell division control protein 42 homolog [KO:K04393]
102225189  cell division control protein 42 homolog isoform X1 [KO:K04393]
102223132  cell division control protein 42 homolog [KO:K04393]
102226130  cell division control protein 42 homolog [KO:K04393]
102225231  dual specificity mitogen-activated protein kinase kinase 4-like isoform X1 [KO:K04430] [EC:2.7.12.2]
102232155  map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]
102238025  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
102237237  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
102226476  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102234094  mitogen-activated protein kinase 8-like isoform X3 [KO:K04440] [EC:2.7.11.24]
102221148  mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102234665  transcription factor AP-1-like [KO:K04448]
102230050  jun; transcription factor AP-1 [KO:K04448]
102231029  gonadotropin subunit beta-2 isoform X1 [KO:K08521]
102222175  cga; glycoprotein hormones alpha chain [KO:K08522]
102222187  gonadotropin subunit beta-1 [KO:K05250]
102220254  ptk2b; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
102237728  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
102226344  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102236291  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
102236856  matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
102236217  hbegf; heparin-binding EGF-like growth factor precursor [KO:K08523]
102236062  epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111606142  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
102228937  melanoma receptor tyrosine-protein kinase [KO:K04361] [EC:2.7.10.1]
102231736  grb2; growth factor receptor-bound protein 2 [KO:K04364]
102232244  sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102234002  sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
102217290  hras; GTPase HRas [KO:K02833]
102233657  kras; GTPase KRas isoform X2 [KO:K07827]
102232995  GTPase HRas-like [KO:K07827]
102234445  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102217036  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102225775  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102235941  mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102237032  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
102227915  elk1; ETS domain-containing protein Elk-1 [KO:K04375]
102217648  egr1; early growth response protein 1 [KO:K09203]
102229961  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
xma04010  MAPK signaling pathway
xma04020  Calcium signaling pathway
xma04060  Cytokine-cytokine receptor interaction
xma04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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