KEGG   PATHWAY: mna04912
Entry
mna04912                    Pathway                                

Name
GnRH signaling pathway - Miniopterus natalensis
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
mna04912  GnRH signaling pathway
mna04912

Organism
Miniopterus natalensis [GN:mna]
Gene
107538045  GNRH1; progonadoliberin-1 [KO:K05252]
107537230  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
107529329  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
107529353  neuroendocrine secretory protein 55-like [KO:K04632]
107526004  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
107540528  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
107534062  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
107531740  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
107527242  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
107528232  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
107531029  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
107539500  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
107535777  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
107544336  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107543188  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107531265  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107544926  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107544328  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
107542967  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
107536366  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
107536369  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
107539797  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
107529142  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
107525255  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
107541588  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
107542429  CALML3; calmodulin-like protein 3 [KO:K02183]
107542435  CALML5; calmodulin-like protein 5 [KO:K02183]
107536794  CALM3; calmodulin [KO:K02183]
107540147  CALML6; calmodulin-like protein 6 [KO:K02183]
107544318  CALM2; calmodulin isoform X1 [KO:K02183]
107531584  CALM1; calmodulin [KO:K02183]
107525969  CALML4; calmodulin-like protein 4 [KO:K02183]
107545830  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
107542053  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
107535228  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
107527851  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
107538300  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
107544745  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
107534935  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
107546425  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
107534931  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
107541372  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
107536018  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
107527145  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
107528582  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
107530487  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
107535728  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
107542219  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
107528394  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
107545565  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107545613  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107536041  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
107536051  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
107524519  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
107546298  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
107536544  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
107536549  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
107536550  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
107536561  cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
107528068  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
107529520  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107533526  phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107542143  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
107538414  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
107540891  cell division control protein 42 homolog [KO:K04393]
107544551  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
107529906  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
107537133  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
107527953  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107528432  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107536966  JUN; transcription factor AP-1 [KO:K04448]
107531805  LHB; lutropin subunit beta [KO:K08521]
107532807  CGA; glycoprotein hormones alpha chain [KO:K08522]
107531918  FSHB; follitropin subunit beta [KO:K05250]
107538557  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
107543503  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
107531691  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
107538002  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
107525996  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
107536618  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
107525851  SOS2; son of sevenless homolog 2 [KO:K03099]
107541780  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
107542351  HRAS; GTPase HRas isoform X1 [KO:K02833]
107525258  KRAS; GTPase KRas [KO:K07827]
107545303  NRAS; GTPase NRas [KO:K07828]
107534729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107533801  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
107525695  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
107541504  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
107530451  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107541393  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
107530099  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
  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
mna04010  MAPK signaling pathway
mna04020  Calcium signaling pathway
mna04024  cAMP signaling pathway
mna04060  Cytokine-cytokine receptor interaction
mna04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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