KEGG   PATHWAY: ptex04912
Entry
ptex04912                   Pathway                                
Name
GnRH signaling pathway - Pseudonaja textilis (eastern brown snake)
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
ptex04912  GnRH signaling pathway
ptex04912

Organism
Pseudonaja textilis (eastern brown snake) [GN:ptex]
Gene
113445669  GNRH1; progonadoliberin-1 [KO:K05252]
113451978  progonadoliberin-2-like [KO:K05252]
113441983  gonadotropin-releasing hormone II receptor-like [KO:K04280]
113447464  LOW QUALITY PROTEIN: gonadotropin-releasing hormone II receptor-like [KO:K04280]
113434327  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
113437370  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
113436537  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
113446325  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
113450840  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
113441153  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
113445503  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
113444984  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
113438325  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
113438988  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
113433613  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
113436070  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
113433792  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
113438459  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
113434991  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
113446578  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
113442603  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
113442692  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
113442728  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
113451193  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
113436405  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
113446972  inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
113447804  inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
113433340  CALM2; calmodulin-2 [KO:K02183]
113445922  CALM3; calmodulin-3 [KO:K02183]
113446254  CALML6; calmodulin-like protein 6 [KO:K02183]
113446645  calmodulin-like [KO:K02183]
113442069  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
113437332  calmodulin-like [KO:K02183]
113444299  CALM1; calmodulin-1 [KO:K02183]
113433811  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
113434772  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
113447676  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
113443011  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
113443192  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
113438611  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
113453193  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
113447447  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
113449745  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
113443408  CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
113446940  voltage-dependent L-type calcium channel subunit alpha-1S-like [KO:K04857]
113447751  voltage-dependent L-type calcium channel subunit alpha-1S-like [KO:K04857]
113446900  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
113441211  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
113447218  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
113447966  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
113439289  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
113438784  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
113436987  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
113445070  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
113445079  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
113446951  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
113446987  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
113447763  mitogen-activated protein kinase 13-like [KO:K04441] [EC:2.7.11.24]
113447794  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
113449965  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
113439154  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113451488  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
113442223  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
113442234  cytosolic phospholipase A2 epsilon-like isoform X1 [KO:K16342] [EC:3.1.1.4]
113438047  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
113438524  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
113438533  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113438543  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113438555  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113438568  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113438574  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
113438593  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
113439766  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
113434410  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
113451601  CDC42; cell division control protein 42 homolog [KO:K04393]
113437210  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
113433617  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
113433784  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
113434600  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
113449402  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113440637  JUN; transcription factor AP-1 [KO:K04448]
113455406  CGA; glycoprotein hormones alpha chain [KO:K08522]
113438856  FSHB; follitropin subunit beta [KO:K05250]
113446316  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
113444987  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
113451750  matrix metalloproteinase-14-like [KO:K07763] [EC:3.4.24.80]
113448731  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
113436503  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
113437354  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
113437138  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
113433387  SOS1; son of sevenless homolog 1 [KO:K03099]
113435148  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
113440320  HRAS; GTPase HRas [KO:K02833]
113441228  KRAS; GTPase KRas isoform X1 [KO:K07827]
113443525  GTPase HRas isoform X1 [KO:K07827]
113444286  NRAS; GTPase NRas [KO:K07828]
113452732  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
113442026  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113450336  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
113446490  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113443485  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
113443232  ELK1; ETS domain-containing protein Elk-1 [KO:K04375]
113454659  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
ptex04010  MAPK signaling pathway
ptex04020  Calcium signaling pathway
ptex04060  Cytokine-cytokine receptor interaction
ptex04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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