KEGG   PATHWAY: gja04912
Entry
gja04912                    Pathway                                
Name
GnRH signaling pathway - Gekko japonicus (Schlegel's Japanese gecko)
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
gja04912  GnRH signaling pathway
gja04912

Organism
Gekko japonicus (Schlegel's Japanese gecko) [GN:gja]
Gene
107118679  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
107124345  GNRH1; gonadotropin releasing hormone 1 [KO:K05252]
107107981  gonadotropin-releasing hormone II receptor-like [KO:K04280]
107123804  gonadotropin-releasing hormone II receptor-like [KO:K04280]
107119835  GNAS; GNAS complex locus [KO:K04632]
107119176  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
107108835  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
107124706  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
107111738  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
107113906  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
107120916  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
107117185  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
107119214  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
107109291  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
107117304  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
107117579  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107117129  ATF4; activating transcription factor 4 [KO:K04374]
107116527  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107120591  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
107106753  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
107115177  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
107123894  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
107119642  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
107116811  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107125949  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107117556  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107117539  CALM3; calmodulin 3 [KO:K02183]
107113282  CALML4; calmodulin like 4 [KO:K02183]
107116092  CALML6; calmodulin like 6 [KO:K02183]
107115205  calmodulin [KO:K02183]
107120542  CALM1; calmodulin 1 [KO:K02183]
107110993  CALM2; calmodulin 2 [KO:K02183]
107110299  calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
107117391  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
107122036  calcium/calmodulin-dependent protein kinase type II subunit gamma-like [KO:K04515] [EC:2.7.11.17]
107123332  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
107106337  protein kinase C beta type-like [KO:K19662] [EC:2.7.11.13]
107115526  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
107120231  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
107116832  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
107117359  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
107110972  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
107123377  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
107117807  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
107116392  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
107113333  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
107120519  dual specificity mitogen-activated protein kinase kinase 3-like [KO:K04432] [EC:2.7.12.2]
107122462  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
107110949  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
107110955  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
107110975  mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
107119112  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107122186  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
107108204  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
107108206  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107108207  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107106952  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107111822  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
107119840  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107119841  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107119842  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107119848  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
107121969  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
107119252  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
107124417  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
107113860  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107109696  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
107116700  CDC42; cell division cycle 42 [KO:K04393]
107123125  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
107117671  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
107114224  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107123710  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
107119264  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
107111867  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
107120418  gonadotropin subunit beta-like [KO:K08521]
107121763  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
107106169  FSHB; follicle stimulating hormone beta subunit [KO:K05250]
107111937  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
107108344  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
107109121  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
107119740  HBEGF; heparin binding EGF like growth factor [KO:K08523]
107119225  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
107110018  GRB2; growth factor receptor bound protein 2 [KO:K04364]
107122628  son of sevenless homolog 2-like [KO:K03099]
107116186  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
107112057  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
107106941  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
107116614  GTPase HRas-like [KO:K07827]
107118023  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
107121194  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
107118240  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
107117455  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107115252  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107115547  ELK1; ELK1, ETS transcription factor [KO:K04375]
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
gja04010  MAPK signaling pathway
gja04020  Calcium signaling pathway
gja04060  Cytokine-cytokine receptor interaction
gja04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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