KEGG   PATHWAY: nmel04912
Entry
nmel04912                   Pathway                                
Name
GnRH signaling pathway - Numida meleagris (helmeted guineafowl)
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
nmel04912  GnRH signaling pathway
nmel04912

Organism
Numida meleagris (helmeted guineafowl) [GN:nmel]
Gene
110387236  GNRH1; progonadoliberin-1 [KO:K05252]
110403519  gonadotropin-releasing hormone II receptor-like isoform X1 [KO:K04280]
110391843  gonadotropin-releasing hormone II receptor-like [KO:K04280]
110403829  putative gonadotropin-releasing hormone II receptor [KO:K04280]
110408305  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
110390836  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
110394300  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
110395965  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
110399200  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
110404374  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
110394336  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
110405807  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
110402971  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
110392532  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110389577  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
110388935  guanine nucleotide-binding protein subunit alpha-11-like isoform X1 [KO:K04635]
110396662  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
110395536  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
110401183  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
110404652  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
110396437  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
110388144  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
110403952  CALML4; calmodulin-like protein 4 [KO:K02183]
110396315  CALM2; calmodulin-2 [KO:K02183]
110401188  CALM1; calmodulin-1 [KO:K02183]
110392216  calmodulin, striated muscle [KO:K02183]
110387161  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
110397346  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
110405364  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
110399309  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
110407228  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
110405777  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
110404811  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
110395457  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
110404743  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
110388201  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
110390387  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
110399799  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
110394259  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
110388470  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
110395417  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
110405901  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
110407251  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
110392503  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
110392504  mitogen-activated protein kinase 12-like isoform X1 [KO:K04441] [EC:2.7.11.24]
110388127  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110388128  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110391499  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
110401265  cytosolic phospholipase A2 beta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
110402446  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
110401489  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110401490  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110401864  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110401865  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110401871  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
110401872  cytosolic phospholipase A2 epsilon-like isoform X1 [KO:K16342] [EC:3.1.1.4]
110401665  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110401676  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
110397970  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
110408003  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
110408527  CDC42; cell division control protein 42 homolog [KO:K04393]
110407172  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
110390478  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
110398630  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110405490  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110399325  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110402812  JUN; transcription factor AP-1 [KO:K04448]
110395287  CGA; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
110401638  FSHB; follitropin subunit beta [KO:K05250]
110395785  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
110404299  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
110405127  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
110393050  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110407421  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
110401960  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110397177  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110400761  HRAS; GTPase HRas [KO:K02833]
110396332  KRAS; GTPase KRas isoform X1 [KO:K07827]
110388133  NRAS; GTPase NRas [KO:K07828]
110404723  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
110404031  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110388854  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110406180  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
110405401  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
nmel04010  MAPK signaling pathway
nmel04020  Calcium signaling pathway
nmel04060  Cytokine-cytokine receptor interaction
nmel04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
LinkDB

DBGET integrated database retrieval system