KEGG   PATHWAY: hai04912
Entry
hai04912                    Pathway                                
Name
GnRH signaling pathway - Hipposideros armiger (great roundleaf 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
hai04912  GnRH signaling pathway
hai04912

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109391730  GNRH1; progonadoliberin-1 [KO:K05252]
109375906  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
109380071  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
109380072  neuroendocrine secretory protein 55 [KO:K04632]
109373011  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
109375976  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
109385186  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
109393593  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
109387200  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
109393238  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
109383261  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
109372359  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
109392133  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
109385440  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
109394225  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
109392248  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
109385746  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109388624  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
109378976  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
109378977  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109384329  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109383976  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109395800  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
109372316  inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
109392407  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
109382670  CALM1; calmodulin [KO:K02183]
109380340  calmodulin-like [KO:K02183]
109391149  CALML6; calmodulin-like protein 6 [KO:K02183]
109383794  calmodulin-like protein 3 [KO:K02183]
109383796  calmodulin-like [KO:K02183]
109372230  CALM3; calmodulin [KO:K02183]
109389917  CALM2; calmodulin [KO:K02183]
109372542  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
109373019  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
109375001  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
109390284  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
109380289  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109395953  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
109388950  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
109395944  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
109374806  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
109380439  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
109385705  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
109371823  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
109380266  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
109394013  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
109390353  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
109371344  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
109395979  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109395980  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396629  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396630  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
109377280  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
109379089  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
109383984  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
109384003  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
109384004  PLA2G4D; LOW QUALITY PROTEIN: cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
109384055  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
109394696  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
109371666  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
109377191  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
109396744  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
109389137  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
109396087  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
109392215  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109377948  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109392748  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109371251  JUN; transcription factor AP-1 [KO:K04448]
109371257  transcription factor AP-1 [KO:K04448]
109390979  lutropin subunit beta isoform X1 [KO:K08521]
109387027  follitropin subunit beta [KO:K05250]
109379535  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
109383663  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
109393698  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
109392466  HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]
109388365  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
109383688  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
109385471  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109375221  SOS2; son of sevenless homolog 2 [KO:K03099]
109375639  HRAS; GTPase HRas isoform X1 [KO:K02833]
109385150  GTPase HRas-like [KO:K02833]
109389264  KRAS; GTPase KRas isoform X1 [KO:K07827]
109377015  NRAS; GTPase NRas [KO:K07828]
109384548  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109376565  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
109392461  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
hai04010  MAPK signaling pathway
hai04020  Calcium signaling pathway
hai04024  cAMP signaling pathway
hai04060  Cytokine-cytokine receptor interaction
hai04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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