KEGG   PATHWAY: fca04912
Entry
fca04912                    Pathway                                
Name
GnRH signaling pathway - Felis catus (domestic cat)
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
fca04912  GnRH signaling pathway
fca04912

Organism
Felis catus (domestic cat) [GN:fca]
Gene
101080783  GNRH1; progonadoliberin-1 isoform X2 [KO:K05252]
102901429  LOW QUALITY PROTEIN: progonadoliberin-2 [KO:K05252]
101088838  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
101098453  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
102900772  neuroendocrine secretory protein 55 [KO:K04632]
101101375  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101094327  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101088157  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101097735  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101100749  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101091211  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101094148  ADCY7; adenylate cyclase type 7 isoform X2 [KO:K08047] [EC:4.6.1.1]
101087555  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101095942  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101084297  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101094708  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X2 [KO:K04634]
101086541  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
101090942  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092961  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101092262  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101090005  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
101100546  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
101101230  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
101087993  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
101081534  CALM2; calmodulin-2 [KO:K02183]
101099307  calmodulin-like protein 3 [KO:K02183]
102902667  calmodulin-like [KO:K02183]
101091063  CALM3; calmodulin-3 [KO:K02183]
101097703  calmodulin-alpha-like [KO:K02183]
101094679  CALM1; calmodulin-1 [KO:K02183]
101086824  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
101100214  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101098221  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X4 [KO:K04515] [EC:2.7.11.17]
101098090  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101084342  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101098615  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
101086433  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101088970  PRKCB; protein kinase C beta type isoform X3 [KO:K19662] [EC:2.7.11.13]
101087716  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101082923  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
101088394  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X8 [KO:K04851]
101080870  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
654399  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
101090328  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
101096406  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
101083633  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X2 [KO:K04421] [EC:2.7.11.25]
101097977  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
101082274  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
101089813  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101097357  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
101082828  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
101082033  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
101083342  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
101082574  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
101082829  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
101084052  PLD1; phospholipase D1 isoform X2 [KO:K01115] [EC:3.1.4.4]
101092214  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
101100378  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101094772  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
101082454  cell division control protein 42 homolog [KO:K04393]
101086432  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101095157  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101097261  JUN; transcription factor AP-1 [KO:K04448]
493833  LHB; lutropin subunit beta precursor [KO:K08521]
751819  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
101084989  FSHB; follitropin subunit beta [KO:K05250]
101091691  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
101098838  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101089776  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
101093578  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
100510799  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
101099916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101098862  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101088847  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas isoform X2 [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
101096047  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101081387  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X3 [KO:K04368] [EC:2.7.12.2]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101095156  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
101088388  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
fca04010  MAPK signaling pathway
fca04020  Calcium signaling pathway
fca04024  cAMP signaling pathway
fca04060  Cytokine-cytokine receptor interaction
fca04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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