KEGG   PATHWAY: pleu04912
Entry
pleu04912                   Pathway                                
Name
GnRH signaling pathway - Peromyscus leucopus (white-footed mouse)
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
pleu04912  GnRH signaling pathway
pleu04912

Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680674  Plcb3; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
114681114  Pla2g4e; LOW QUALITY PROTEIN: cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
114681118  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
114681139  Pla2g4d; cytosolic phospholipase A2 delta isoform X2 [KO:K16342] [EC:3.1.1.4]
114681142  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
114681418  Calm3; calmodulin-3 [KO:K02183]
114681520  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
114681621  Sos1; son of sevenless homolog 1 [KO:K03099]
114681835  Src; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
114682025  [KO:K04632]
114682029  [KO:K04632]
114682227  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114683276  Map2k3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]
114683277  Mapk7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
114683299  Cacna1s; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
114684152  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114684224  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
114684635  [KO:K08521]
114685127  [KO:K02833]
114686066  Map2k7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
114686204  Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114687550  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
114687991  [KO:K04374]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114688160  Gna11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
114688488  [KO:K02833]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114690404  Map3k3; mitogen-activated protein kinase kinase kinase 3 isoform X3 [KO:K04421] [EC:2.7.11.25]
114690439  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114690458  Map2k6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
114691309  [KO:K04393]
114691364  Map3k4; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114691640  Calml4; calmodulin-like protein 4 isoform X2 [KO:K02183]
114691643  Map3k2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
114691777  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
114691978  Itpr1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958]
114692203  Prkcb; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114693019  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
114693020  Mapk11; mitogen-activated protein kinase 11 isoform X5 [KO:K04441] [EC:2.7.11.24]
114693118  Map2k4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
114693493  [KO:K02833]
114693595  Hras; GTPase HRas isoform X1 [KO:K02833]
114693768  Jun; transcription factor AP-1 [KO:K04448]
114693962  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
114693978  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X7 [KO:K04515] [EC:2.7.11.17]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114694533  Mmp2; LOW QUALITY PROTEIN: 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
114696121  Adcy2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
114696553  [KO:K02833]
114696773  Pla2g4a; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
114696911  [KO:K04634]
114697107  Adcy3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
114697206  Cdc42; cell division control protein 42 homolog isoform X1 [KO:K04393]
114697539  Pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
114697724  Adcy8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
114698264  Prkacb; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114698582  Nras; GTPase NRas [KO:K07828]
114699348  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
114699415  Cga; glycoprotein hormones alpha chain [KO:K08522]
114700207  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114700762  Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C isoform X8 [KO:K04850]
114701275  [KO:K04393]
114701281  Cacna1f; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]
114702097  Fshb; LOW QUALITY PROTEIN: follitropin subunit beta [KO:K05250]
114702701  Gnrh1; progonadoliberin-1 [KO:K05252]
114702950  Map3k1; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
114703666  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
114703672  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
114703899  Pla2g4c; cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]
114703932  Elk1; ETS domain-containing protein Elk-1 isoform X2 [KO:K04375]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114704841  Adcy5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114705020  Calm1; calmodulin-1 [KO:K02183]
114705134  Hbegf; proheparin-binding EGF-like growth factor [KO:K08523]
114705532  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114705921  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
114706123  Itpr3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
114706162  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
114706165  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
114707024  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
114707316  Ptk2b; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
114707396  Camk2a; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
114708186  Prkcd; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
114708260  Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
114708393  Itpr2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
114708477  Kras; GTPase KRas isoform X2 [KO:K07827]
114708501  Adcy7; LOW QUALITY PROTEIN: adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
114708522  Adcy6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
114708701  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
114708709  Mmp14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
114708768  [KO:K02183]
114708779  Calml3; calmodulin-like protein 3 [KO:K02183]
114709126  Gnrhr; gonadotropin-releasing hormone receptor isoform X1 [KO:K04280]
114709209  Calm2; calmodulin-2 [KO:K02183]
114710523  [KO:K04371] [EC:2.7.11.24]
114710615  Adcy9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
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
pleu04010  MAPK signaling pathway
pleu04020  Calcium signaling pathway
pleu04024  cAMP signaling pathway
pleu04060  Cytokine-cytokine receptor interaction
pleu04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

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