KEGG   PATHWAY: myd04912
Entry
myd04912                    Pathway                                
Name
GnRH signaling pathway - Myotis davidii (David's myotis)
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
myd04912  GnRH signaling pathway
myd04912

Organism
Myotis davidii (David's myotis) [GN:myd]
Gene
102763285  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
102753420  GNRH1; gonadotropin releasing hormone 1 [KO:K05252]
102770612  GNRHR; gonadotropin releasing hormone receptor [KO:K04280]
102774843  guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632]
102775507  neuroendocrine secretory protein 55 [KO:K04632]
102759978  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102774384  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102757252  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102762536  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102760678  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102766123  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102764043  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102765722  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102760324  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102759840  cGMP-dependent protein kinase 1 [KO:K04345] [EC:2.7.11.11]
102772218  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102773780  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102763654  ATF4; activating transcription factor 4 [KO:K04374]
102760847  GNAQ; G protein subunit alpha q [KO:K04634]
102771954  GNA11; G protein subunit alpha 11 [KO:K04635]
102751685  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102751959  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102755123  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102760520  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102755292  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102764661  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102754756  CALM1; calmodulin 1 [KO:K02183]
102772033  CALM3; calmodulin 3 [KO:K02183]
102772812  CALML3; calmodulin like 3 [KO:K02183]
102773102  CALML5; calmodulin like 5 [KO:K02183]
102756281  CALM2; calmodulin 2 [KO:K02183]
102772521  CALML6; calmodulin like 6 [KO:K02183]
102764405  calmodulin-like [KO:K02183]
102755062  CALML4; calmodulin like 4 [KO:K02183]
102765684  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102773049  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102764742  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102765661  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102757004  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102760591  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102753812  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102761441  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102771414  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102760374  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102763786  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
102753581  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
102762787  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
102757393  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
102765923  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102759247  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102770309  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102770021  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102755728  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102756012  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102769984  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102754320  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102754611  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
102774327  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102771796  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102772466  JMJD7; jumonji domain containing 7 [KO:K16342] [EC:3.1.1.4]
102760085  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102756028  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102769511  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102758165  CDC42; cell division cycle 42 [KO:K04393]
102769098  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102760954  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102772062  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102764416  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102775351  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107183844  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102752693  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102769451  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
102752503  FSHB; follicle stimulating hormone beta subunit [KO:K05250]
102756394  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102767174  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
102761559  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
102751834  HBEGF; heparin binding EGF like growth factor [KO:K08523]
102775204  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102754991  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102768105  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102763262  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102762537  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102762284  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102761492  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102772748  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102763997  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102757282  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102769037  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102775211  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102755127  ELK1; ELK1, ETS transcription factor [KO:K04375]
102759696  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
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
myd04010  MAPK signaling pathway
myd04020  Calcium signaling pathway
myd04024  cAMP signaling pathway
myd04060  Cytokine-cytokine receptor interaction
myd04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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