KEGG   PATHWAY: gga04912
Entry
gga04912                    Pathway                                
Name
GnRH signaling pathway - Gallus gallus (chicken)
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
gga04912  GnRH signaling pathway
gga04912

Organism
Gallus gallus (chicken) [GN:gga]
Gene
770134  GNRH1; progonadoliberin-1 precursor [KO:K05252]
427517  GNRHR; gonadotropin-releasing hormone II receptor [KO:K04280]
395368  CGNRHRL; gonadotropin-releasing hormone receptor-like [KO:K04280]
419313  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
420788  ADCY1; adenylate cyclase type 1 isoform X2 [KO:K08041] [EC:4.6.1.1]
420935  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
422013  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
395340  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
107050028  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
415732  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
420328  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
395339  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
424542  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X7 [KO:K04345] [EC:2.7.11.11]
395693  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
427262  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
374077  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
423014  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
416730  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
427687  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
395412  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
418212  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
419910  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
396523  CALM1; neo-calmodulin [KO:K02183]
416692  CALML3; calmodulin, striated muscle [KO:K02183]
395855  CALM2; calmodulin [KO:K02183]
427515  CALML4; calmodulin-like protein 4 [KO:K02183]
374174  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
374175  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
423737  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
422688  CAMK2D; calcium/calmodulin-dependent protein kinase type II delta chain [KO:K04515] [EC:2.7.11.17]
417430  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
416567  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
415905  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
395891  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
395895  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
395985  CATSPER2; voltage-dependent L-type calcium channel subunit alpha-1S isoform 1 [KO:K04857]
427144  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
424225  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
419954  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
420419  MAPKKK3L; mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
421579  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
416496  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
417445  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
417739  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
421183  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
769763  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
771145  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100858386  uncharacterized protein LOC100858386 isoform X1 [KO:K04464] [EC:2.7.11.24]
423227  PLA2G4EL6; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
396394  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
428870  PLA2G4EL3; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
771574  PLA2G4EL2; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
428871  PLA2G4F; cytosolic phospholipase A2 zeta isoform X2 [KO:K16342] [EC:3.1.1.4]
771560  PLA2G4EL4; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
423229  PLA2G4EL1; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
423226  PLA2G4EL7; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
771552  PLA2G4EL5; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
101749229  PLA2G4B; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
424986  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
396442  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
395917  CDC42; cell division control protein 42 homolog precursor [KO:K04393]
417312  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
107050551  dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
423778  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
395983  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
422592  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
424673  JUN; transcription factor AP-1 [KO:K04448]
421829  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
374108  FSHB; follitropin subunit beta precursor [KO:K05250]
421998  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
386583  MMP2; 72 kDa type IV collagenase preproprotein [KO:K01398] [EC:3.4.24.24]
395654  HBEGF; proheparin-binding EGF-like growth factor precursor [KO:K08523]
396494  EGFR; epidermal growth factor receptor precursor [KO:K04361] [EC:2.7.10.1]
386572  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
423572  SOS2; son of sevenless homolog 2 [KO:K03099]
431192  SOS1; son of sevenless homolog 1 [KO:K03099]
396229  HRAS; GTPase HRas precursor [KO:K02833]
418207  KRAS; GTPase KRas [KO:K07827]
419885  NRAS; GTPase NRas precursor [KO:K07828]
396245  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
415549  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
396349  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
373953  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
373931  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
gga04010  MAPK signaling pathway
gga04020  Calcium signaling pathway
gga04060  Cytokine-cytokine receptor interaction
gga04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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