KEGG   PATHWAY: cfa04912
Entry
cfa04912                    Pathway                                
Name
GnRH signaling pathway - Canis lupus familiaris (dog)
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
cfa04912  GnRH signaling pathway
cfa04912

Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
608671  GNRH1; progonadoliberin-1 [KO:K05252]
102151131  uncharacterized protein LOC102151131 [KO:K05252]
403718  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
403943  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
607357  ADCY1; LOW QUALITY PROTEIN: adenylate cyclase type 1 isoform X5 [KO:K08041] [EC:4.6.1.1]
478624  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
482994  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
480271  ADCY4; adenylate cyclase type 4 isoform X2 [KO:K08044] [EC:4.6.1.1]
403859  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
477625  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
487289  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
482045  ADCY8; adenylate cyclase type 8 isoform X2 [KO:K08048] [EC:4.6.1.1]
490031  ADCY9; adenylate cyclase type 9 isoform X2 [KO:K08049] [EC:4.6.1.1]
403556  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
479975  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X2 [KO:K04345] [EC:2.7.11.11]
474503  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
403928  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
403914  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
477160  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
485773  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
476034  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858] [EC:3.1.4.11]
100856190  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
476548  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
486628  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X2 [KO:K04959]
481746  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
474584  CALM2; calmodulin-2 [KO:K02183]
607269  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
487146  CALML5; calmodulin-like protein 5 [KO:K02183]
480416  CALM1; calmodulin-1 [KO:K02183]
476428  CALM3; calmodulin-3 isoform X2 [KO:K02183]
478351  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
102153034  calmodulin-like protein 3 [KO:K02183]
489050  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
610764  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
612941  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
482687  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
490904  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
489968  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
494005  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
403516  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X17 [KO:K04850]
484724  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X15 [KO:K04851]
480915  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
490244  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X2 [KO:K04857]
478061  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
612902  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
480481  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X8 [KO:K04421] [EC:2.7.11.25]
476262  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
489547  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
480454  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
403856  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
607019  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
607023  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
612821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
489532  MAPK7; mitogen-activated protein kinase 7 isoform X2 [KO:K04464] [EC:2.7.11.24]
487514  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
480048  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
487512  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
487515  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
608811  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
488167  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
479473  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
485864  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
119863888  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
119866928  cell division control protein 42 homolog [KO:K04393]
489508  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
485004  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
477746  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
478464  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
474652  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
609429  JUN; transcription factor AP-1 [KO:K04448]
403483  CGA; glycoprotein hormones alpha chain precursor [KO:K08522]
485428  FSHB; follitropin subunit beta [KO:K05250]
486102  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
403733  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
403823  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
607007  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
404306  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
483312  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
490682  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
403735  HRAS; GTPase HRas isoform 1 [KO:K02833]
403871  KRAS; GTPase KRas isoform X1 [KO:K07827]
403872  NRAS; GTPase NRas [KO:K07828]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
478347  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
611939  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
491860  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
481528  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
cfa04010  MAPK signaling pathway
cfa04020  Calcium signaling pathway
cfa04024  cAMP signaling pathway
cfa04060  Cytokine-cytokine receptor interaction
cfa04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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