KEGG   PATHWAY: ray04912
Entry
ray04912                    Pathway                                
Name
GnRH signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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
ray04912  GnRH signaling pathway
ray04912

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107512528  GNRH1; progonadoliberin-1 [KO:K05252]
107520510  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
107500068  neuroendocrine secretory protein 55-like [KO:K04632]
107500067  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
107512406  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
107502700  ADCY2; LOW QUALITY PROTEIN: adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
107498506  ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
107498014  ADCY4; LOW QUALITY PROTEIN: adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
107518038  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
107514224  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
107512248  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
107497689  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
107521680  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
107519437  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107511590  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107500816  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107517194  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107520124  GNA11; LOW QUALITY PROTEIN: guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
107506114  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
107519930  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
107497081  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
107514464  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
107504134  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
107497427  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
107511965  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107509556  CALM2; calmodulin [KO:K02183]
107508927  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
107515457  CALM1; calmodulin [KO:K02183]
107516034  CALM3; calmodulin [KO:K02183]
107501627  calmodulin-like protein 5 [KO:K02183]
107510894  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
107512385  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
107497167  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
107498266  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
107510307  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
107516091  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
107516555  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
107500540  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
107516535  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
107514999  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
107513628  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
107518617  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
107516884  MAP3K2; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
107501901  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
107514741  MAP3K4; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
107506757  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
107510279  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107511070  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
107514503  cytosolic phospholipase A2 beta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
107521615  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
107510914  PLA2G4E; LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
107510922  LOW QUALITY PROTEIN: cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
107510924  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
107510925  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
107515926  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107509491  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
107512598  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
107513058  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
107517401  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
107519926  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107498874  lutropin subunit beta [KO:K08521]
107501740  CGA; glycoprotein hormones alpha chain [KO:K08522]
107515744  FSHB; follitropin subunit beta [KO:K05250]
107515459  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
107499669  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
107498042  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
107521572  HBEGF; LOW QUALITY PROTEIN: proheparin-binding EGF-like growth factor [KO:K08523]
107498193  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
107503781  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
107519446  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107511436  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107509357  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
107518733  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
ray04010  MAPK signaling pathway
ray04020  Calcium signaling pathway
ray04024  cAMP signaling pathway
ray04060  Cytokine-cytokine receptor interaction
ray04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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