KEGG   PATHWAY: aful04912
Entry
aful04912                   Pathway                                
Name
GnRH signaling pathway - Aythya fuligula (tufted duck)
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
aful04912  GnRH signaling pathway
aful04912

Organism
Aythya fuligula (tufted duck) [GN:aful]
Gene
116499441  GNRH1; progonadoliberin-1 [KO:K05252]
116493544  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116493733  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116499802  gonadotropin-releasing hormone II receptor-like [KO:K04280]
116495569  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
116486732  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
116488201  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
116490539  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116499930  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
116494191  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
116486321  ADCY8; LOW QUALITY PROTEIN: adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
116495186  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
116491750  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116501070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116501065  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116501389  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
116498997  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
116487397  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
116487565  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
116490387  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
116492888  ITPR1; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
116488562  ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
116498720  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
116487273  CALM2; calmodulin-2 [KO:K02183]
116493714  CALML4; calmodulin-like protein 4 [KO:K02183]
116489394  CALM1; calmodulin-1 [KO:K02183]
116501561  calmodulin-beta-like [KO:K02183]
116501563  calmodulin-like [KO:K02183]
116501770  calmodulin, striated muscle [KO:K02183]
116489100  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
116494874  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
116491384  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116496571  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116495441  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116492904  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
116489537  CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
116493152  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
116501486  voltage-dependent L-type calcium channel subunit alpha-1F-like [KO:K04853]
116498683  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
116501197  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
116501286  LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 1-like [KO:K04416] [EC:2.7.11.25]
116490728  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
116486750  mitogen-activated protein kinase kinase kinase 3-like isoform X1 [KO:K04421] [EC:2.7.11.25]
116498376  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
116487327  MAP3K4; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
116495505  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
116496466  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
116498684  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
116489834  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
116489843  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
116491943  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
116498294  PLA2G4C; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
116489567  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116489876  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116489886  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116489887  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116489921  cytosolic phospholipase A2 beta-like [KO:K16342] [EC:3.1.1.4]
116489997  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
116490054  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116490067  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
116492324  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
116495903  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
116497501  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
116496474  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
116489162  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116495022  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116491194  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116492142  JUN; transcription factor AP-1 [KO:K04448]
116488181  CGA; glycoprotein hormones alpha chain [KO:K08522]
116490081  FSHB; follitropin subunit beta [KO:K05250]
116487529  PTK2B; LOW QUALITY PROTEIN: protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
116493904  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
116494807  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
116485864  EGFR; LOW QUALITY PROTEIN: epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
116496483  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
116487382  SOS1; son of sevenless homolog 1 [KO:K03099]
116489737  SOS2; son of sevenless homolog 2 [KO:K03099]
116490064  HRAS; GTPase HRas [KO:K02833]
116486326  KRAS; LOW QUALITY PROTEIN: GTPase KRas [KO:K07827]
116498924  NRAS; GTPase NRas [KO:K07828]
116493064  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116493377  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
116499043  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116496022  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116494907  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
aful04010  MAPK signaling pathway
aful04020  Calcium signaling pathway
aful04060  Cytokine-cytokine receptor interaction
aful04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
LinkDB

DBGET integrated database retrieval system