KEGG   PATHWAY: npr04912
Entry
npr04912                    Pathway                                
Name
GnRH signaling pathway - Nanorana parkeri (Xizang Plateau frog)
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
npr04912  GnRH signaling pathway
npr04912

Organism
Nanorana parkeri (Xizang Plateau frog) [GN:npr]
Gene
108794701  progonadoliberin-1-like [KO:K05252]
108798892  GNRH2; progonadoliberin-2 [KO:K05252]
108799806  gonadotropin-releasing hormone II receptor-like [KO:K04280]
108791980  gonadotropin-releasing hormone II receptor-like [KO:K04280]
108798813  gonadotropin-releasing hormone II receptor-like [KO:K04280]
108802775  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
108784456  guanine nucleotide-binding protein G(s) subunit alpha-like [KO:K04632]
108796974  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
108795542  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
108788450  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
108801019  adenylate cyclase type 5-like [KO:K08045] [EC:4.6.1.1]
108802250  adenylate cyclase type 6-like [KO:K08046] [EC:4.6.1.1]
108794932  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
108788952  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
108790811  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
108784350  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
108790539  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
108791874  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
108787585  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
108788493  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
108791250  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
108789286  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
108793965  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108795563  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
108795338  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108791910  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
108786728  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
108787281  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
108799395  calmodulin-alpha-like [KO:K02183]
108784100  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
108804514  CALM2; calmodulin [KO:K02183]
108788690  CALM1; calmodulin isoform X1 [KO:K02183]
108804479  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108785806  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
108785601  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
108798063  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
108791355  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
108797915  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
108791575  voltage-dependent L-type calcium channel subunit alpha-1C-like isoform X1 [KO:K04850]
108786047  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
108788491  LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
108804869  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
108792018  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
108785393  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
108784622  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
108802493  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
108795048  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
108804838  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
108804839  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
108787378  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108788240  mitogen-activated protein kinase 12-like [KO:K04441] [EC:2.7.11.24]
108800678  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
108798704  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
108789917  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
108793921  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
108789293  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
108800202  phospholipase D2-like [KO:K01115] [EC:3.1.4.4]
108784828  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
108787987  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
108797397  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
108801499  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
108790540  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108794648  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108804455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108788164  JUN; transcription factor AP-1 [KO:K04448]
108802167  lutropin subunit beta [KO:K08521]
108785310  CGA; glycoprotein hormones alpha chain [KO:K08522]
108796389  FSHB; follitropin subunit beta [KO:K05250]
108801309  protein-tyrosine kinase 2-beta-like [KO:K05871] [EC:2.7.10.2]
108797889  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
108786770  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
108799381  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
108799518  epidermal growth factor receptor-like [KO:K04361] [EC:2.7.10.1]
108791159  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
108788949  SOS1; son of sevenless homolog 1 [KO:K03099]
108795074  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
108786689  HRAS; GTPase HRas [KO:K02833]
108797553  KRAS; GTPase KRas isoform X1 [KO:K07827]
108803002  GTPase HRas-like [KO:K07827]
108799544  NRAS; GTPase NRas [KO:K07828]
108787573  RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
108784101  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108794889  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108801239  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
108798115  EGR1; early growth response protein 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
npr04010  MAPK signaling pathway
npr04020  Calcium signaling pathway
npr04060  Cytokine-cytokine receptor interaction
npr04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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