KEGG   PATHWAY: ccae04912
Entry
ccae04912                   Pathway                                
Name
GnRH signaling pathway - Cyanistes caeruleus (blue tit)
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
ccae04912  GnRH signaling pathway
ccae04912

Organism
Cyanistes caeruleus (blue tit) [GN:ccae]
Gene
111938829  GNRH1; progonadoliberin-1 [KO:K05252]
111933979  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
111938030  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
111923918  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
111925673  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
111932249  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111940536  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
111934618  ADCY7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
111925137  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
111925138  adenylate cyclase type 8-like [KO:K08048] [EC:4.6.1.1]
111935874  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
111932863  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111934860  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
111940710  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
111940370  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
111926455  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
111926460  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
111930495  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
111934931  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
111930014  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
111939798  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
111927637  calmodulin [KO:K02183]
111929893  CALM1; calmodulin-1 [KO:K02183]
111923171  calmodulin, striated muscle [KO:K02183]
111943688  calmodulin-like protein 4 [KO:K02183]
111935541  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
111928996  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111931070  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111945916  calcium/calmodulin-dependent protein kinase type II subunit beta-like [KO:K04515] [EC:2.7.11.17]
111937433  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111936199  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111935183  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
111928486  voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
111935128  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111939717  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
111941445  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
111932210  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
111939927  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
111925531  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
111926951  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
111936127  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
111937452  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
111922987  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
111923053  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
111939795  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111939796  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111932478  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
111930078  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930079  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930080  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
111930225  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930226  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930228  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930229  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111930230  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
111933332  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
111938254  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
111938571  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
111937201  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
111922673  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
111928823  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111935562  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111931141  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
111932998  JUN; transcription factor AP-1 [KO:K04448]
111926069  CGA; glycoprotein hormones alpha chain [KO:K08522]
111930471  FSHB; follitropin subunit beta [KO:K05250]
111927477  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
111934584  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
111945170  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
111923657  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
111937316  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
111929515  SOS2; son of sevenless homolog 2 [KO:K03099]
111926571  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
111930717  HRAS; GTPase HRas [KO:K02833]
111945773  KRAS; GTPase KRas isoform X1 [KO:K07827]
111939625  NRAS; GTPase NRas [KO:K07828]
111935240  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
111933966  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
111940193  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
111936534  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111935419  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
ccae04010  MAPK signaling pathway
ccae04020  Calcium signaling pathway
ccae04060  Cytokine-cytokine receptor interaction
ccae04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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