KEGG   PATHWAY: epz04912
Entry
epz04912                    Pathway                                
Name
GnRH signaling pathway - Equus przewalskii (Przewalski's horse)
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
epz04912  GnRH signaling pathway
epz04912

Organism
Equus przewalskii (Przewalski's horse) [GN:epz]
Gene
103540947  [KO:K05250]
103540948  FSHB; LOW QUALITY PROTEIN: follitropin subunit beta [KO:K05250]
103541899  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
103542193  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
103542405  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103543290  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103543382  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
103543808  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
103543955  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103544963  CALM3; calmodulin-3 [KO:K02183]
103546037  GNRH1; progonadoliberin-1 isoform X1 [KO:K05252]
103546360  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
103546514  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
103546580  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103546629  KRAS; GTPase KRas isoform X1 [KO:K07827]
103546630  ITPR2; inositol 1,4,5-trisphosphate-gated calcium channel ITPR2 isoform X1 [KO:K04959]
103547036  [KO:K04632]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103547763  CGA; glycoprotein hormones alpha chain [KO:K08522]
103547823  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103548212  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103548885  CALML5; calmodulin-like protein 5 [KO:K02183]
103548886  [KO:K02183]
103549121  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
103549414  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103549465  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
103549616  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
103549630  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
103549765  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
103549905  CALM1; calmodulin-1 isoform X1 [KO:K02183]
103549946  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
103549947  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
103549950  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
103549953  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
103550297  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform X1 [KO:K04958]
103550428  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
103550430  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103551354  EGR1; early growth response protein 1 [KO:K09203]
103552675  NRAS; GTPase NRas [KO:K07828]
103552793  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
103553014  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103553088  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103553197  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
103553307  [KO:K08521]
103553450  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
103553980  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103554541  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103554952  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103556123  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103556184  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X6 [KO:K04428] [EC:2.7.11.25]
103556230  [KO:K04280]
103556685  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
103556751  MMP14; matrix metalloproteinase-14 isoform X2 [KO:K07763] [EC:3.4.24.80]
103557289  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103558105  CALM2; calmodulin-2 [KO:K02183]
103558165  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103558482  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
103559485  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103559491  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
103559733  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
103560072  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
103560128  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
103560664  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
103560754  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103560907  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
103561050  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103561633  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
103562194  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103562440  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
103562505  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
103563092  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103563198  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
103563634  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103563810  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103563830  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
103564053  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
103564566  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X2 [KO:K04433] [EC:2.7.12.2]
103564724  ITPR3; inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 isoform X1 [KO:K04960]
103565109  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103565289  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103565402  [KO:K04632]
103565534  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103565868  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
103565953  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103567332  HRAS; GTPase HRas isoform X1 [KO:K02833]
103567415  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
103567623  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
103567629  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103567795  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
139081849  [KO:K02183]
139081876  JUN; transcription factor Jun [KO:K04448]
139085032  [KO:K07827]
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
epz04010  MAPK signaling pathway
epz04020  Calcium signaling pathway
epz04024  cAMP signaling pathway
epz04060  Cytokine-cytokine receptor interaction
epz04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

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