KEGG   PATHWAY: rfq04912
Entry
rfq04912                    Pathway                                
Name
GnRH signaling pathway - Rhinolophus ferrumequinum (greater horseshoe bat)
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
rfq04912  GnRH signaling pathway
rfq04912

Organism
Rhinolophus ferrumequinum (greater horseshoe bat) [GN:rfq]
Gene
117012187  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
117012276  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
117012305  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
117012818  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
117013296  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
117013305  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
117013390  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
117013460  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
117013546  [KO:K02183]
117013633  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
117013636  [KO:K02833]
117013723  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
117013904  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
117014282  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
117014672  NRAS; GTPase NRas [KO:K07828]
117015705  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
117015708  [KO:K04632]
117015790  [KO:K05252]
117015870  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
117015911  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
117015942  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
117016461  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
117016634  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
117016683  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
117016939  EGR1; early growth response protein 1 [KO:K09203]
117016991  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
117017296  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117018399  [KO:K04432] [EC:2.7.12.2]
117018578  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
117018595  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
117019182  [KO:K02183]
117019237  [KO:K02183]
117019414  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117019474  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
117020093  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
117020427  CGA; glycoprotein hormones alpha chain [KO:K08522]
117020595  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
117020871  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
117022220  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
117022409  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
117022803  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
117022823  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
117022841  CALM1; calmodulin-1 [KO:K02183]
117022939  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
117022968  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117023033  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
117023064  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
117023696  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
117024110  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
117024113  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
117024169  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
117025090  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
117025303  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
117025443  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
117026302  [KO:K04440] [EC:2.7.11.24]
117026472  CALML6; calmodulin-like protein 6 [KO:K02183]
117026985  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
117027001  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
117027175  JUN; transcription factor AP-1 [KO:K04448]
117028134  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117028303  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
117028439  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
117028978  KRAS; GTPase KRas isoform X1 [KO:K07827]
117029085  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
117029232  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
117029264  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
117029835  HRAS; LOW QUALITY PROTEIN: GTPase HRas [KO:K02833]
117030205  FSHB; follitropin subunit beta [KO:K05250]
117030619  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
117031053  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
117031869  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
117032856  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
117032869  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
117033010  CALM2; calmodulin-2 [KO:K02183]
117033942  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
117034378  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
117034828  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
117034856  CALM3; calmodulin-3 [KO:K02183]
117035241  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
117035828  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
117035933  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
117036785  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
117037173  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
117037221  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
117037259  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117037515  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
117037602  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
117037633  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
117037761  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
117037860  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
117038075  CAMK2D; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
117038360  GNRH1; progonadoliberin-1 [KO:K05252]
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
rfq04010  MAPK signaling pathway
rfq04020  Calcium signaling pathway
rfq04024  cAMP signaling pathway
rfq04060  Cytokine-cytokine receptor interaction
rfq04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

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