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
103555821  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
103552793  GNRHR; gonadotropin releasing hormone receptor [KO:K04280]
103556230  gonadotropin-releasing hormone II receptor-like [KO:K04280]
103565402  guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103547036  neuroendocrine secretory protein 55 [KO:K04632]
103550430  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103562505  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
103547823  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103561050  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103563830  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103563634  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103556685  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103565019  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
103567623  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103553014  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103557289  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103565953  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103565289  ATF4; activating transcription factor 4 [KO:K04374]
103553450  GNAQ; G protein subunit alpha q [KO:K04634]
103543382  guanine nucleotide-binding protein subunit alpha-11-like [KO:K04635]
103562440  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103559733  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103561633  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103542193  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103550297  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103546630  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103548182  inositol 1,4,5-trisphosphate receptor type 2-like [KO:K04959]
103564724  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103548885  CALML5; calmodulin like 5 [KO:K02183]
103548886  CALML3; calmodulin like 3 [KO:K02183]
103549905  CALM1; calmodulin 1 [KO:K02183]
103558105  CALM2; calmodulin 2 [KO:K02183]
103564053  calmodulin-like protein 4 [KO:K02183]
103544963  calmodulin-alpha-like [KO:K02183]
103567415  CALML6; calmodulin like 6 [KO:K02183]
103549465  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103549616  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103549121  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103554952  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103558165  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103546514  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103560754  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103543955  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103565109  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103548212  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103562194  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
103549765  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
103556184  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
103563092  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103564566  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
103565534  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103563198  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103559485  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103559491  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103565868  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
103549946  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103549947  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103549950  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103549953  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103560072  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103546360  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
103560664  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
103560907  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103558482  CDC42; cell division cycle 42 [KO:K04393]
103567795  dual specificity mitogen-activated protein kinase kinase 4-like [KO:K04430] [EC:2.7.12.2]
103543808  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103549414  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103553980  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103567629  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103553307  LHB; luteinizing hormone beta polypeptide [KO:K08521]
103547763  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
103540947  FSHB; follicle stimulating hormone beta subunit [KO:K05250]
103540948  follitropin subunit beta-like [KO:K05250]
103550428  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
103553197  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
103556751  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
103548009  HBEGF; heparin binding EGF like growth factor [KO:K08523]
103560128  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103546580  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103553088  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103556123  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103567332  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103546629  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103552675  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103554541  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103549630  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103543290  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
103547261  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103562408  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103551354  EGR1; early growth response 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
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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