KEGG   PATHWAY: uar04912
Entry
uar04912                    Pathway                                
Name
GnRH signaling pathway - Ursus americanus (American black bear)
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
uar04912  GnRH signaling pathway
uar04912

Organism
Ursus americanus (American black bear) [GN:uar]
Gene
123799117  progonadoliberin-2 [KO:K05252]
123777375  GNRH1; progonadoliberin-1 [KO:K05252]
123778685  gonadotropin-releasing hormone II receptor [KO:K04280]
123775890  GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]
123803297  neuroendocrine secretory protein 55 [KO:K04632]
123803290  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
123789481  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
123791264  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
123799951  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
123795737  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
123802178  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
123794794  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
123798393  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
123801897  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
123783548  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
123801768  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
123795272  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123780649  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123781527  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
123793965  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
123799710  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
123799736  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
123804253  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
123778465  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
123799165  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
123801684  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
123790908  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
123785908  CALM2; calmodulin-2 [KO:K02183]
123800842  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
123802291  calmodulin-like [KO:K02183]
123802321  CALML3; calmodulin-like protein 3 [KO:K02183]
123796079  CALML6; calmodulin-like protein 6 [KO:K02183]
123798898  CALM1; calmodulin-1 [KO:K02183]
123778741  CALM3; calmodulin-3 [KO:K02183]
123793341  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
123803651  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
123789460  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
123782837  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
123803224  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
123778823  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
123798757  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
123777895  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
123798762  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
123797184  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
123785763  CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
123790179  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
123779518  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X1 [KO:K04420] [EC:2.7.11.25]
123802932  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
123797538  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
123779716  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
123803240  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
123803776  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
123803793  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
123776209  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
123776212  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
123779755  MAPK7; LOW QUALITY PROTEIN: mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
123801377  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
123803827  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
123803837  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
123775802  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
123776483  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
123792197  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
123786391  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
123796968  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
123803163  cell division control protein 42 homolog [KO:K04393]
123782153  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
123792071  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
123777544  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
123800287  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
123788054  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
123790496  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
123795376  JUN; transcription factor AP-1 [KO:K04448]
123776350  LHB; lutropin subunit beta [KO:K08521]
123776172  CGA; glycoprotein hormones alpha chain [KO:K08522]
123799532  follitropin subunit beta [KO:K05250]
123777394  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
123798414  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
123795799  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
123790277  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
123786270  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
123802938  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123799809  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123793291  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
123775506  HRAS; GTPase HRas isoform X1 [KO:K02833]
123801699  KRAS; GTPase KRas isoform X1 [KO:K07827]
123795037  NRAS; GTPase NRas [KO:K07828]
123802053  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123800861  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
123796818  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123795639  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
123784602  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123787940  ELK1; LOW QUALITY PROTEIN: ETS domain-containing protein Elk-1 [KO:K04375]
123790304  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
uar04010  MAPK signaling pathway
uar04020  Calcium signaling pathway
uar04024  cAMP signaling pathway
uar04060  Cytokine-cytokine receptor interaction
uar04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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