KEGG   PATHWAY: pvp04912
Entry
pvp04912                    Pathway                                
Name
GnRH signaling pathway - Pteropus vampyrus (large 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
pvp04912  GnRH signaling pathway
pvp04912

Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288668  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
105288669  PLA2G4F; cytosolic phospholipase A2 zeta isoform X2 [KO:K16342] [EC:3.1.1.4]
105288781  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105288785  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
105288787  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105288866  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515] [EC:2.7.11.17]
105288933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105289326  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
105289628  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
105289813  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105290127  CALM1; calmodulin-1 [KO:K02183]
105290433  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
105291271  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X4 [KO:K04430] [EC:2.7.12.2]
105291313  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
105291755  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
105292047  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
105292087  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
105292218  GNRH1; progonadoliberin-1 [KO:K05252]
105292221  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
105292442  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
105292913  CALM2; calmodulin-2 isoform X1 [KO:K02183]
105292949  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105293353  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105293621  EGR1; early growth response protein 1 [KO:K09203]
105293714  FSHB; follitropin subunit beta [KO:K05250]
105294059  KRAS; GTPase KRas isoform X2 [KO:K07827]
105294112  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105294444  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
105295052  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
105295171  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105296083  [KO:K04632]
105296513  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105296550  NRAS; GTPase NRas isoform X1 [KO:K07828]
105296936  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
105296996  CGA; glycoprotein hormones alpha chain isoform X2 [KO:K08522]
105297298  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
105297322  CALM3; calmodulin-3 [KO:K02183]
105297518  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105297702  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105297731  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X3 [KO:K04421] [EC:2.7.11.25]
105297846  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105298737  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105298936  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
105299021  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105299180  [KO:K02183]
105299360  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
105299441  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
105299444  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105299581  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105299978  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105300436  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
105300520  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
105301035  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105301036  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
105301042  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
105301250  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
105301757  [KO:K08521]
105302452  [KO:K04634]
105302767  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
105303095  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105303606  CALML6; calmodulin-like protein 6 [KO:K02183]
105304165  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
105304348  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
105304363  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
105304566  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105305461  ELK1; ETS domain-containing protein Elk-1 isoform X1 [KO:K04375]
105305679  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
105305933  HRAS; GTPase HRas isoform X1 [KO:K02833]
105306010  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
105306141  [KO:K04361] [EC:2.7.10.1]
105306744  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105306966  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
105307700  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
105308283  [KO:K04441] [EC:2.7.11.24]
105308299  [KO:K08041] [EC:4.6.1.1]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
105308762  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
105308818  [KO:K19662] [EC:2.7.11.13]
105309056  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
105309400  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105309535  SOS2; son of sevenless homolog 2 [KO:K03099]
105309689  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105309827  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
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
pvp04010  MAPK signaling pathway
pvp04020  Calcium signaling pathway
pvp04024  cAMP signaling pathway
pvp04060  Cytokine-cytokine receptor interaction
pvp04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

DBGET integrated database retrieval system