KEGG   PATHWAY: lve04912
Entry
lve04912                    Pathway                                

Name
GnRH signaling pathway - Lipotes vexillifer (Yangtze River dolphin)
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
lve04912  GnRH signaling pathway
lve04912

Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103070213  GNRH1; gonadotropin releasing hormone 1 [KO:K05252]
103085292  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
103074337  putative gonadotropin-releasing hormone II receptor-like [KO:K04280]
103079467  GNRHR; gonadotropin releasing hormone receptor [KO:K04280]
103089051  GNAS; GNAS complex locus [KO:K04632]
103085385  neuroendocrine secretory protein 55-like [KO:K04632]
103081539  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103084817  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103076182  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103075499  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103091169  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103075153  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
103078677  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103085845  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103070451  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103077464  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103074112  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103083306  ATF4; activating transcription factor 4 [KO:K04374]
103082420  GNAQ; G protein subunit alpha q [KO:K04634]
103076924  GNA11; G protein subunit alpha 11 [KO:K04635]
103086280  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103083884  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103078639  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103079287  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
103079294  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
103078697  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
103070387  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
103091655  CALM3; calmodulin 3 [KO:K02183]
103079915  CALML6; calmodulin like 6 [KO:K02183]
103080762  CALM1; calmodulin 1 [KO:K02183]
103087479  CALM2; calmodulin 2 [KO:K02183]
103072156  CALML4; calmodulin like 4 [KO:K02183]
103074541  calmodulin-like protein 1-like [KO:K02183]
103074817  CALML5; calmodulin like 5 [KO:K02183]
103088458  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103075213  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103072903  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103081366  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103073028  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103090549  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103073166  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103087340  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
103074544  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
103082192  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
103090575  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
103083385  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103083140  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
103076636  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
103075844  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
103091611  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
103081641  dual specificity mitogen-activated protein kinase kinase 6-like [KO:K04433] [EC:2.7.12.2]
103083209  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103077530  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103078049  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103078710  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103080813  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
103090681  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103090934  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103089071  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103083510  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103083784  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103069742  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
103084538  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
103072342  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103088294  CDC42; cell division cycle 42 [KO:K04393]
103091203  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
103091499  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103084630  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103087676  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103078792  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103071861  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103086103  LHB; luteinizing hormone beta polypeptide [KO:K08521]
103072990  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
103074712  follitropin subunit beta-like [KO:K05250]
103083166  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
103071760  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
103081188  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
103074900  HBEGF; heparin binding EGF like growth factor [KO:K08523]
103071962  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
103079766  GRB2; growth factor receptor bound protein 2 [KO:K04364]
103079242  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103081084  SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
103076043  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103077579  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103068734  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103087933  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103082805  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103090769  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103070260  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103091628  ELK1; ELK1, ETS transcription factor [KO:K04375]
103090503  EGR1; early growth response 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
  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
  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
  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
  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
  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
  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
  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
  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
  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
lve04010  MAPK signaling pathway
lve04020  Calcium signaling pathway
lve04024  cAMP signaling pathway
lve04060  Cytokine-cytokine receptor interaction
lve04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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