KEGG   PATHWAY: pale04912
Entry
pale04912                   Pathway                                
Name
GnRH signaling pathway - Pteropus alecto (black flying fox)
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
pale04912  GnRH signaling pathway
pale04912

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102878247  GNRH1; progonadoliberin-1 [KO:K05252]
102880174  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
102889764  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
102884106  neuroendocrine secretory protein 55-like [KO:K04632]
102887497  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102893265  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
102886232  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
102890575  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102897495  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102890588  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
102881535  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
102896789  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102885676  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
102886679  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102877853  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102896553  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102877919  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102888619  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102879238  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
102885207  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
102885781  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
102885953  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
102894982  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102896356  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102881783  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102894226  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102897273  CALM3; calmodulin-3 [KO:K02183]
102886058  CALM1; calmodulin-1 [KO:K02183]
102884196  CALML6; calmodulin-like protein 6 [KO:K02183]
102891673  calmodulin-like [KO:K02183]
102893109  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102881744  calmodulin-like [KO:K02183]
102888982  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
102888385  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102880869  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102896030  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
102887078  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102880663  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102888600  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102882682  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X2 [KO:K04850]
102888351  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102893611  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
102896136  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
102886741  MAP3K1; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
102880422  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
102889570  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
102888506  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
102886389  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
102888822  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102895900  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888602  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102888845  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102877720  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102897014  MAPK7; mitogen-activated protein kinase 7 isoform X2 [KO:K04464] [EC:2.7.11.24]
102883421  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102883684  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X2 [KO:K16342] [EC:3.1.1.4]
102887778  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102886310  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102888274  cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
102884736  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
102894598  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
102891249  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
102889114  CDC42; cell division control protein 42 homolog [KO:K04393]
102894945  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X3 [KO:K04430] [EC:2.7.12.2]
102892533  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102885064  MAPK10; mitogen-activated protein kinase 10 isoform X5 [KO:K04440] [EC:2.7.11.24]
102890689  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102892777  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102896121  JUN; transcription factor AP-1 [KO:K04448]
102884710  lutropin subunit beta [KO:K08521]
102890788  CGA; glycoprotein hormones alpha chain [KO:K08522]
102897414  FSHB; follitropin subunit beta [KO:K05250]
102886432  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
102883808  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102887003  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
102882842  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102878877  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
102892713  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
pale04010  MAPK signaling pathway
pale04020  Calcium signaling pathway
pale04024  cAMP signaling pathway
pale04060  Cytokine-cytokine receptor interaction
pale04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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