KEGG   PATHWAY: pmua04912
Entry
pmua04912                   Pathway                                
Name
GnRH signaling pathway - Podarcis muralis (common wall lizard)
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
pmua04912  GnRH signaling pathway
pmua04912

Organism
Podarcis muralis (common wall lizard) [GN:pmua]
Gene
114604364  progonadoliberin-2 [KO:K05252]
114586268  gonadotropin-releasing hormone II receptor-like [KO:K04280]
114584373  gonadotropin-releasing hormone II receptor-like [KO:K04280]
114599685  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
114607043  ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]
114601220  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114594931  adenylate cyclase type 3-like [KO:K08043] [EC:4.6.1.1]
114581737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
114603889  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
114592965  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
114602227  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
114600245  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114584296  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
114598815  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114590804  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114605162  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114606268  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
114588282  guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
114593658  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114593659  PLCB4; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
114593800  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114586167  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
114591812  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114604922  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114599227  ITPR3; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114583951  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
114602546  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
114587213  calmodulin [KO:K02183]
114594763  CALM2; calmodulin-2 [KO:K02183]
114605532  calmodulin-A-like isoform X1 [KO:K02183]
114605533  calmodulin-like [KO:K02183]
114591081  CALM1; calmodulin-1 isoform X1 [KO:K02183]
114603269  CALM3; calmodulin-3 [KO:K02183]
114591346  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
114597036  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114585935  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
114604777  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114588142  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
114583925  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114589765  protein kinase C delta type-like [KO:K06068] [EC:2.7.11.13]
114591604  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
114605885  voltage-dependent L-type calcium channel subunit alpha-1C-like [KO:K04850]
114591684  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114587594  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
114599194  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
114606892  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
114603537  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
114607438  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
114581713  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
114594310  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
114584096  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
114588447  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
114599205  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114599208  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114605285  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114605047  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
114582827  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
114582942  LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
114589436  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
114582080  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114584040  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
114581922  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
114594296  PLA2G4F; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
114594260  cytosolic phospholipase A2 epsilon-like isoform X1 [KO:K16342] [EC:3.1.1.4]
114594270  cytosolic phospholipase A2 epsilon-like isoform X1 [KO:K16342] [EC:3.1.1.4]
114594287  cytosolic phospholipase A2 delta-like isoform X1 [KO:K16342] [EC:3.1.1.4]
114588340  LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
114582772  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114594233  cytosolic phospholipase A2 delta-like [KO:K16342] [EC:3.1.1.4]
114598629  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
114585925  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
114582346  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
114597981  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
114582880  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
114599561  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
114602591  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
114590704  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
114590811  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
114596969  MAPK8; LOW QUALITY PROTEIN: mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
114603995  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114591317  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
114598927  JUN; transcription factor AP-1 [KO:K04448]
114583739  lutropin subunit beta-like [KO:K08521]
114593929  CGA; glycoprotein hormones alpha chain isoform X1 [KO:K08522]
114585054  FSHB; follitropin subunit beta [KO:K05250]
114594952  PTK2B; LOW QUALITY PROTEIN: protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
114602200  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
114581663  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
114601160  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
114607096  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114590607  growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
114591118  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
114594815  SOS1; son of sevenless homolog 1 [KO:K03099]
114599845  HRAS; GTPase HRas isoform X1 [KO:K02833]
114608097  GTPase HRas-like [KO:K07827]
114605215  KRAS; GTPase KRas isoform X1 [KO:K07827]
114599398  NRAS; GTPase NRas [KO:K07828]
114591641  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114584876  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
114588247  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114586322  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114582021  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114587683  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
114591481  EGR1; LOW QUALITY PROTEIN: 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
pmua04010  MAPK signaling pathway
pmua04020  Calcium signaling pathway
pmua04060  Cytokine-cytokine receptor interaction
pmua04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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