KEGG   PATHWAY: cjc04912
Entry
cjc04912                    Pathway                                

Name
GnRH signaling pathway - Callithrix jacchus (white-tufted-ear marmoset)
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
cjc04912  GnRH signaling pathway
cjc04912

Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100409186  GNRH1; gonadotropin releasing hormone 1 [KO:K05252]
103792807  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
100385305  GNRHR; gonadotropin releasing hormone receptor [KO:K04280]
100399755  GNRHR2; gonadotropin-releasing hormone II receptor-like [KO:K04280]
100408515  GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]
103787209  neuroendocrine secretory protein 55 [KO:K04632]
100394265  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100385658  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100415165  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100415141  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100412782  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100406617  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
100404620  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100404484  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100405403  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100392123  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100407753  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100408115  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
100407692  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100400737  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100392193  ATF4; activating transcription factor 4 [KO:K04374]
100403006  GNAQ; G protein subunit alpha q [KO:K04634]
100386734  GNA11; G protein subunit alpha 11 [KO:K04635]
100400803  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100386921  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100409716  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100410075  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100385763  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
100390843  inositol 1,4,5-trisphosphate receptor type 3-like [KO:K04960]
100390180  CALM1; calmodulin 1 [KO:K02183]
100386819  CALM2; calmodulin 2 [KO:K02183]
100406081  CALM3; calmodulin 3 [KO:K02183]
100408289  CALML3; calmodulin like 3 [KO:K02183]
100407929  CALML5; calmodulin like 5 [KO:K02183]
100392199  CALML6; calmodulin like 6 [KO:K02183]
100396690  CALML4; calmodulin like 4 [KO:K02183]
100397956  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
100405903  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
100391424  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
100390938  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
100410352  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
100391814  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
100410136  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100395399  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
100406735  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
100397940  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
100386041  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
100390112  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
100389500  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
100406711  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
100409608  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
100413660  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
100398593  MAP2K3; mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
100397389  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
100396611  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100396967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100404377  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100405093  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100400023  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
100391709  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
100400789  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
100401154  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
100402439  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
100397093  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
100391217  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
100386165  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
100404291  CDC42; cell division cycle 42 [KO:K04393]
100386168  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
100412930  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
100392721  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100387686  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100390109  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100400411  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100391685  CGB; chorionic gonadotropin, beta polypeptide [KO:K08521]
100389264  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
100398993  FSHB; follicle stimulating hormone beta subunit [KO:K05250]
100404210  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
100387448  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
100389088  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
100392997  HBEGF; heparin binding EGF like growth factor [KO:K08523]
100412158  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
100395682  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100414931  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
100410124  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
100406017  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
100414782  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
100415300  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100387394  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100393991  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100400700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100404815  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100393766  ELK1; ELK1, ETS transcription factor [KO:K04375]
100406530  EGR1; early growth response 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
  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
  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
  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
  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
  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
  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
  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
  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
  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
cjc04010  MAPK signaling pathway
cjc04020  Calcium signaling pathway
cjc04024  cAMP signaling pathway
cjc04060  Cytokine-cytokine receptor interaction
cjc04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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