KEGG   PATHWAY: alim04912
Entry
alim04912                   Pathway                                
Name
GnRH signaling pathway - Austrofundulus limnaeus (annual killifish)
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
alim04912  GnRH signaling pathway
alim04912

Organism
Austrofundulus limnaeus (annual killifish) [GN:alim]
Gene
106526701  gnrh1; progonadoliberin-1 [KO:K05252]
106523583  gnrh2; progonadoliberin-2 [KO:K05252]
106513273  progonadoliberin-3-like [KO:K05252]
106514329  gonadotropin-releasing hormone II receptor-like [KO:K04280]
106524272  putative gonadotropin-releasing hormone II receptor [KO:K04280]
106536564  gonadotropin-releasing hormone II receptor-like [KO:K04280]
106518979  gonadotropin-releasing hormone II receptor-like [KO:K04280]
106513057  gnas; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
106515123  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632]
106533941  adenylate cyclase type 1-like isoform X1 [KO:K08041] [EC:4.6.1.1]
106532267  adenylate cyclase type 1-like [KO:K08041] [EC:4.6.1.1]
106516755  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
106514248  adenylate cyclase type 2-like isoform X1 [KO:K08042] [EC:4.6.1.1]
106530667  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
106527078  adenylate cyclase type 4-like isoform X1 [KO:K08044] [EC:4.6.1.1]
106524252  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
106525241  adenylate cyclase type 6-like isoform X1 [KO:K08046] [EC:4.6.1.1]
106530128  adcy5; adenylate cyclase type 5 [KO:K08046] [EC:4.6.1.1]
106527041  adenylate cyclase type 2-like [KO:K08047] [EC:4.6.1.1]
106527219  adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
106531266  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
106532502  adenylate cyclase type 9-like isoform X1 [KO:K08049] [EC:4.6.1.1]
106518708  adcy9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
106511338  prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
106526233  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
106534672  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
106533807  cAMP-dependent protein kinase catalytic subunit beta-like isoform X1 [KO:K04345] [EC:2.7.11.11]
106522498  atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106534845  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
106516252  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04634]
106523804  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
106521552  guanine nucleotide-binding protein subunit alpha-11-like isoform X1 [KO:K04635]
106528393  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
106519799  plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
106524973  plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
106529251  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1-like [KO:K05858] [EC:3.1.4.11]
106518551  plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
106518553  plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
106518058  inositol 1,4,5-trisphosphate receptor type 1-like [KO:K04958]
106527163  inositol 1,4,5-trisphosphate receptor type 1-like [KO:K04958]
106515612  itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
106527884  LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
106527471  calmodulin [KO:K02183]
106526330  calmodulin [KO:K02183]
106515407  calm3; calmodulin [KO:K02183]
106526525  calmodulin-like [KO:K02183]
106512977  calml4; calmodulin-like protein 4 [KO:K02183]
106523895  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
106530901  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
106533117  calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
106516639  calcium/calmodulin-dependent protein kinase type II subunit gamma-like isoform X1 [KO:K04515] [EC:2.7.11.17]
106531119  calcium/calmodulin-dependent protein kinase type II delta 2 chain isoform X1 [KO:K04515] [EC:2.7.11.17]
106515369  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
106536360  calcium/calmodulin-dependent protein kinase type II delta 1 chain-like [KO:K04515] [EC:2.7.11.17]
106524495  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
106519470  calcium/calmodulin-dependent protein kinase type II delta chain-like [KO:K04515] [EC:2.7.11.17]
106518739  protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
106534248  prkcb; protein kinase C beta type isoform X1 [KO:K02677] [EC:2.7.11.13]
106519663  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
106516520  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
106518011  prkcd; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
106515158  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
106513069  cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
106516186  voltage-dependent L-type calcium channel subunit alpha-1D-like isoform X1 [KO:K04851]
106533880  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
106519282  cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
106523414  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
106525038  cacna1s; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
106531440  map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
106513381  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
106534689  map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
106518124  map3k4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
106528548  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
106529047  dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
106523196  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
106513331  mitogen-activated protein kinase 14B isoform X1 [KO:K04441] [EC:2.7.11.24]
106525575  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
106531213  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
106531214  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
106525512  mitogen-activated protein kinase 14B-like isoform X1 [KO:K04441] [EC:2.7.11.24]
106518909  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
106521362  mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
106529930  cytosolic phospholipase A2 gamma-like isoform X1 [KO:K16342] [EC:3.1.1.4]
106529932  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
106516826  pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
106516375  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
106525543  pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
106516318  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
106533758  phospholipase D1-like [KO:K01115] [EC:3.1.4.4]
106533680  src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
106512030  proto-oncogene tyrosine-protein kinase Src-like [KO:K05704] [EC:2.7.10.2]
106528512  cell division control protein 42 homolog isoform X1 [KO:K04393]
106519594  cell division control protein 42 homolog [KO:K04393]
106519316  cell division control protein 42 homolog isoform X1 [KO:K04393]
106529148  cell division control protein 42 homolog [KO:K04393]
106531926  dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
106535063  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
106515295  map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
106516220  mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
106524736  mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
106517558  mitogen-activated protein kinase 9-like isoform X1 [KO:K04440] [EC:2.7.11.24]
106534447  transcription factor AP-1-like [KO:K04448]
106521291  jun; transcription factor AP-1 [KO:K04448]
106528952  gonadotropin subunit beta-2 [KO:K08521]
106521971  cga; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
106523543  fshb; follitropin subunit beta [KO:K05250]
106529652  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
106525285  ptk2b; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
106517245  mmp2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
106517892  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
106526432  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
106535469  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
106516002  proheparin-binding EGF-like growth factor [KO:K08523]
106531647  melanoma receptor tyrosine-protein kinase-like [KO:K04361] [EC:2.7.10.1]
106533007  egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
106523871  growth factor receptor-bound protein 2 [KO:K04364]
106528413  sos2; son of sevenless homolog 2 [KO:K03099]
106536500  son of sevenless homolog 1-like [KO:K03099]
106515650  hras; GTPase HRas [KO:K02833]
106515615  kras; GTPase KRas isoform X1 [KO:K07827]
106528169  GTPase HRas-like [KO:K07827]
106519055  raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106521211  map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106515024  map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106537032  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
106530982  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106516482  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
106532784  ETS domain-containing protein Elk-3-like [KO:K04375]
106510834  egr1; early growth response protein 1 [KO:K09203]
106531503  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
alim04010  MAPK signaling pathway
alim04020  Calcium signaling pathway
alim04060  Cytokine-cytokine receptor interaction
alim04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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