KEGG   PATHWAY: dro04912
Entry
dro04912                    Pathway                                
Name
GnRH signaling pathway - Desmodus rotundus (common vampire 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
dro04912  GnRH signaling pathway
dro04912

Organism
Desmodus rotundus (common vampire bat) [GN:dro]
Gene
112305202  GNRH1; progonadoliberin-1 [KO:K05252]
112320151  GNRHR; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
112303826  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112303827  neuroendocrine secretory protein 55-like [KO:K04632]
112306844  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
112321008  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112297750  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
112300586  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
112320488  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
112318673  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
112296774  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
112315487  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
112298360  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112309395  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
112301523  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
112321682  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112300359  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
112312418  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
112304122  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
112311437  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
112304255  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
112317151  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
112309625  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
112318382  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
112302101  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
112322988  CALML3; calmodulin-like protein 3 [KO:K02183]
112311702  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
112311250  CALM1; calmodulin-1 [KO:K02183]
112321120  calmodulin-like [KO:K02183]
112312926  CALM3; calmodulin-3 [KO:K02183]
112299615  CALML6; calmodulin-like protein 6 [KO:K02183]
112301078  calmodulin-beta-like [KO:K02183]
112297939  CALM2; calmodulin-2 [KO:K02183]
112305463  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
112306861  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
112312435  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
112319561  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
112316515  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
112304830  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
112301220  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
112309331  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
112301160  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
112322357  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
112318756  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
112315269  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
112313010  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
112316249  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
112297294  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
112308621  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
112316519  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
112302047  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
112321896  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
112302140  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
112322057  mitogen-activated protein kinase 11-like [KO:K04441] [EC:2.7.11.24]
112308530  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
112296687  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
112311060  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
112311538  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
112311539  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
112308502  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
112307458  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
112303920  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
112299195  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
112308830  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
112305131  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
112296379  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
112305558  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
112317841  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
112314642  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
112310212  lutropin subunit beta [KO:K08521]
112297422  CGA; glycoprotein hormones alpha chain [KO:K08522]
112303242  FSHB; follitropin subunit beta [KO:K05250]
112312413  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
112296673  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
112301504  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
112318203  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
112306912  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
112298645  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
112297971  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
112310995  SOS2; son of sevenless homolog 2 [KO:K03099]
112317099  HRAS; GTPase HRas isoform X1 [KO:K02833]
112318275  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
112304041  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
112313707  NRAS; GTPase NRas [KO:K07828]
112301126  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
112311345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
112312483  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
112304801  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
112301746  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
112322485  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
112318120  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
dro04010  MAPK signaling pathway
dro04020  Calcium signaling pathway
dro04024  cAMP signaling pathway
dro04060  Cytokine-cytokine receptor interaction
dro04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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