KEGG PATHWAY: ocu04912

KEGG

PATHWAY: ocu04912

Entry

ocu04912                    Pathway

Name

GnRH signaling pathway - Oryctolagus cuniculus (rabbit)

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

GnRH signaling pathway

Organism

Oryctolagus cuniculus (rabbit) [GN:ocu]

Gene

progonadoliberin-1 [KO:K05252]

GNRHR; gonadotropin-releasing hormone receptor [KO:K04280]

guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]

neuroendocrine secretory protein 55 [KO:K04632]

adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]

adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]

adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]

adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]

ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]

adenylate cyclase type 6 isoform X8 [KO:K08046] [EC:4.6.1.1]

adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]

adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]

adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]

PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]

cAMP-dependent protein kinase catalytic subunit beta isoform X3 [KO:K04345] [EC:2.7.11.11]

cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]

guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]

inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]

inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959]

inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]

LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]

calmodulin-like protein 3 [KO:K02183]

calmodulin-3 [KO:K02183]

CALM2; calmodulin [KO:K02183]

calmodulin-1 [KO:K02183]

calmodulin-like protein 4 isoform X1 [KO:K02183]

calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]

calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]

CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]

CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]

PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]

PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]

protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]

CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]

CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]

voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853]

CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]

mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]

mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]

mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]

mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]

dual specificity mitogen-activated protein kinase kinase 3 isoform X3 [KO:K04432] [EC:2.7.12.2]

dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]

mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]

mitogen-activated protein kinase 7 isoform X2 [KO:K04464] [EC:2.7.11.24]

PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]

cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]

cytosolic phospholipase A2 delta isoform X2 [KO:K16342] [EC:3.1.1.4]

PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]

PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]

cytosolic phospholipase A2 gamma isoform X1 [KO:K16342] [EC:3.1.1.4]

phospholipase D1 [KO:K01115] [EC:3.1.4.4]

phospholipase D2 [KO:K01115] [EC:3.1.4.4]

proto-oncogene tyrosine-protein kinase Src isoform X1 [KO:K05704] [EC:2.7.10.2]

cell division control protein 42 homolog isoform X1 [KO:K04393]

cell division control protein 42 homolog [KO:K04393]

dual specificity mitogen-activated protein kinase kinase 4 isoform X2 [KO:K04430] [EC:2.7.12.2]

dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]

mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]

mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]

mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]

JUN; transcription factor Jun [KO:K04448]

LHB; lutropin subunit beta precursor [KO:K08521]

CGA; glycoprotein hormones alpha chain precursor [KO:K08522]

FSHB; follitropin subunit beta precursor [KO:K05250]

protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]

MMP2; 72 kDa type IV collagenase precursor [KO:K01398] [EC:3.4.24.24]

MMP14; matrix metalloproteinase-14 precursor [KO:K07763] [EC:3.4.24.80]

proheparin-binding EGF-like growth factor [KO:K08523]

epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]

growth factor receptor-bound protein 2 [KO:K04364]

son of sevenless homolog 1 isoform X1 [KO:K03099]

son of sevenless homolog 2 isoform X1 [KO:K03099]

GTPase HRas isoform X1 [KO:K02833]

GTPase KRas isoform X1 [KO:K07827]

GTPase KRas-like [KO:K07827]

GTPase NRas [KO:K07828]

RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1-like [KO:K04368] [EC:2.7.12.2]

mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

ETS domain-containing protein Elk-1 [KO:K04375]

early growth response protein 1 [KO:K09203]

Compound

Calcium cation

Diacylglycerol

Arachidonate

Phosphatidate

3',5'-Cyclic AMP

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

MAPK signaling pathway

Calcium signaling pathway

cAMP signaling pathway

Cytokine-cytokine receptor interaction

Neuroactive ligand-receptor interaction

KO pathway

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