KEGG   PATHWAY: lcm04912
Entry
lcm04912                    Pathway                                
Name
GnRH signaling pathway - Latimeria chalumnae (coelacanth)
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
lcm04912  GnRH signaling pathway
lcm04912

Organism
Latimeria chalumnae (coelacanth) [GN:lcm]
Gene
102359356  GNRH2; gonadotropin releasing hormone 2 [KO:K05252]
102366752  GNRHR1/III; gonadotropin-releasing hormone II receptor-like [KO:K04280]
102355733  GnRHRI; gonadotropin-releasing hormone receptor-like [KO:K04280]
102363373  GNRHR2/nmI; gonadotropin-releasing hormone II receptor-like [KO:K04280]
102346610  GNRHR3/II; gonadotropin-releasing hormone II receptor-like [KO:K04280]
102364206  GNRHR; gonadotropin releasing hormone receptor [KO:K04280]
102352483  GNAS; GNAS complex locus [KO:K04632]
102367170  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
102365947  adenylate cyclase type 2-like [KO:K08042] [EC:4.6.1.1]
102353581  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102366154  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102351065  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102346737  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102363182  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102359855  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102362951  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102365086  ATF4; activating transcription factor 4 [KO:K04374]
102359416  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
102352409  GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04634]
102365542  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102345855  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102348275  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102362364  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102361301  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
102359880  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
102349825  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
102345989  parvalbumin beta-like [KO:K02183]
102366907  CALML6; calmodulin like 6 [KO:K02183]
102360791  calmodulin [KO:K02183]
102347246  CALM1; calmodulin 1 [KO:K02183]
102359711  CALM2; calmodulin 2 [KO:K02183]
102361286  calmodulin [KO:K02183]
102359693  CALML4; calmodulin like 4 [KO:K02183]
102360263  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
102361646  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102346458  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102360076  calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
102361415  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102364971  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102367474  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102357941  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
102360815  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
102353236  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
102356715  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
102355070  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
102350566  MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]
102353974  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
102350357  mitogen-activated protein kinase kinase kinase 3-like [KO:K04421] [EC:2.7.11.25]
102366133  MAP3K4; mitogen-activated protein kinase kinase kinase 4 [KO:K04428] [EC:2.7.11.25]
102351267  MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 [KO:K04432] [EC:2.7.12.2]
102362389  MAP2K6; mitogen-activated protein kinase kinase 6 [KO:K04433] [EC:2.7.12.2]
102354316  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102354774  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102358042  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102358623  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102351206  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
102356324  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
102352898  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102360293  cytosolic phospholipase A2 gamma-like [KO:K16342] [EC:3.1.1.4]
102359218  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102353212  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102360542  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102358869  CDC42; cell division cycle 42 [KO:K04393]
102352547  MAP2K4; mitogen-activated protein kinase kinase 4 [KO:K04430] [EC:2.7.12.2]
102365163  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102357573  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102351693  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102351958  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102350279  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102358101  transcription factor AP-1-like [KO:K04448]
102360885  LHB; lutropin subunit beta [KO:K08521]
102359455  CGA; glycoprotein hormones, alpha polypeptide [KO:K08522]
102364762  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102350008  MMP2; matrix metallopeptidase 2 [KO:K01398] [EC:3.4.24.24]
102355301  MMP14; matrix metallopeptidase 14 [KO:K07763] [EC:3.4.24.80]
102353749  HBEGF; heparin binding EGF like growth factor [KO:K08523]
102353904  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102347108  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102348404  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102355427  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102352473  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102357700  GTPase HRas-like [KO:K07827]
102361045  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102357545  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102358560  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102350370  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102355992  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102354262  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102363355  ETS domain-containing protein Elk-1-like [KO:K04375]
102351917  ELK1; ELK1, ETS transcription factor [KO:K04375]
102366110  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
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
lcm04010  MAPK signaling pathway
lcm04020  Calcium signaling pathway
lcm04060  Cytokine-cytokine receptor interaction
lcm04080  Neuroactive ligand-receptor interaction
KO pathway
ko04912   
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