KEGG   PATHWAY: cmy04912
Entry
cmy04912                    Pathway                                
Name
GnRH signaling pathway - Chelonia mydas (green sea turtle)
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
cmy04912  GnRH signaling pathway
cmy04912

Organism
Chelonia mydas (green sea turtle) [GN:cmy]
Gene
102929430  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
102929489  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
102929883  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102930460  [KO:K02183]
102930552  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
102930570  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
102930792  [KO:K16342] [EC:3.1.1.4]
102930804  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
102930962  [KO:K04345] [EC:2.7.11.11]
102931046  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858] [EC:3.1.4.11]
102931327  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102931357  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102931360  CGA; glycoprotein hormones alpha chain [KO:K08522]
102931453  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
102931859  [KO:K04421] [EC:2.7.11.25]
102932045  CALM1; calmodulin-1 isoform X2 [KO:K02183]
102932254  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
102932325  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X9 [KO:K04431] [EC:2.7.12.2]
102932555  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102932606  GNRH1; progonadoliberin-1 [KO:K05252]
102932835  MAPK10; mitogen-activated protein kinase 10 isoform X4 [KO:K04440] [EC:2.7.11.24]
102932986  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102933326  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:2.7.10.1]
102933404  [KO:K02183]
102933975  [KO:K05252]
102934181  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
102934282  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
102934468  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102934812  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
102934859  MAPK14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
102935187  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102935217  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X13 [KO:K04515] [EC:2.7.11.17]
102935773  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
102936228  MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]
102936869  [KO:K16342] [EC:3.1.1.4]
102937094  [KO:K16342] [EC:3.1.1.4]
102937264  JUN; transcription factor AP-1 [KO:K04448]
102937309  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102937323  [KO:K16342] [EC:3.1.1.4]
102937453  CALML6; calmodulin-like protein 6 [KO:K02183]
102937534  [KO:K04345] [EC:2.7.11.11]
102937553  [KO:K16342] [EC:3.1.1.4]
102937758  [KO:K04345] [EC:2.7.11.11]
102937778  [KO:K16342] [EC:3.1.1.4]
102938087  MAPK11; mitogen-activated protein kinase 11 isoform X6 [KO:K04441] [EC:2.7.11.24]
102938233  [KO:K16342] [EC:3.1.1.4]
102938366  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
102938448  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
102938664  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102939135  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
102939145  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960]
102939355  [KO:K04280]
102939584  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X2 [KO:K04432] [EC:2.7.12.2]
102939716  SRC; proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]
102940198  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102940215  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102941281  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
102941290  FSHB; follitropin subunit beta isoform X2 [KO:K05250]
102941338  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
102941356  MAP3K2; mitogen-activated protein kinase kinase kinase 2 isoform X2 [KO:K04420] [EC:2.7.11.25]
102941364  KRAS; GTPase KRas isoform X1 [KO:K07827]
102941584  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
102941618  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
102941719  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X2 [KO:K04958]
102941988  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102942020  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
102942074  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
102942096  EGR1; early growth response protein 1 [KO:K09203]
102942183  ADCY6; LOW QUALITY PROTEIN: adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
102942218  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
102942246  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X8 [KO:K05858] [EC:3.1.4.11]
102942399  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102942754  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]
102942934  [KO:K16342] [EC:3.1.1.4]
102942953  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102943017  [KO:K07827]
102943021  [KO:K04280]
102943305  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102943947  MMP14; matrix metalloproteinase-14 [KO:K07763] [EC:3.4.24.80]
102944545  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
102945306  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102945547  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102945664  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
102945804  ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
102945827  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]
102945932  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102945967  [KO:K04280]
102946066  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
102946407  ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
102946454  HRAS; GTPase HRas [KO:K02833]
102946725  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
102947195  CALM2; calmodulin-2 [KO:K02183]
102947444  CALML4; calmodulin-like protein 4 [KO:K02183]
102947510  [KO:K16342] [EC:3.1.1.4]
102947735  [KO:K16342] [EC:3.1.1.4]
114020321  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857]
119564375  CALM3; calmodulin-3 [KO:K02183]
119564816  [KO:K04345] [EC:2.7.11.11]
119567853  [KO:K16342] [EC:3.1.1.4]
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
cmy04010  MAPK signaling pathway
cmy04020  Calcium signaling pathway
cmy04060  Cytokine-cytokine receptor interaction
cmy04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   

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