KEGG PATHWAY: cabi04912

KEGG

PATHWAY: cabi04912

Entry

cabi04912                   Pathway

Name

GnRH signaling pathway - Chelonoidis abingdonii (Abingdon island giant tortoise)

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

Chelonoidis abingdonii (Abingdon island giant tortoise) [GN:cabi]

Gene

CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]

CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]

MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]

CALM1; calmodulin-1 [KO:K02183]

NRAS; GTPase NRas [KO:K07828]

ELK1; ETS domain-containing protein Elk-1 [KO:K04375]

ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]

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

CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]

[KO:K04345] [EC:2.7.11.11]

ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]

CALM2; calmodulin-2 [KO:K02183]

PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]

MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]

MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]

MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

CGA; glycoprotein hormones alpha chain [KO:K08522]

CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]

RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]

PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]

HRAS; GTPase HRas [KO:K02833]

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

MAP3K1; LOW QUALITY PROTEIN: mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]

[KO:K16342] [EC:3.1.1.4]

SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]

PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]

PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]

MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]

CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]

FSHB; follitropin subunit beta [KO:K05250]

ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]

GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635]

CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]

[KO:K04515] [EC:2.7.11.17]

[KO:K04345] [EC:2.7.11.11]

MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]

ADCY9; adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]

GNAS; guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632]

MAP2K3; dual specificity mitogen-activated protein kinase kinase 3 isoform X1 [KO:K04432] [EC:2.7.12.2]

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

PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]

ADCY7; adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]

ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]

ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]

[KO:K04421] [EC:2.7.11.25]

EGR1; early growth response protein 1 [KO:K09203]

ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]

MAP3K2; mitogen-activated protein kinase kinase kinase 2 [KO:K04420] [EC:2.7.11.25]

KRAS; GTPase KRas isoform X1 [KO:K07827]

ADCY3; LOW QUALITY PROTEIN: adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]

PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]

SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]

[KO:K16342] [EC:3.1.1.4]

GRB2; growth factor receptor-bound protein 2 [KO:K04364]

MAP3K4; mitogen-activated protein kinase kinase kinase 4 isoform X1 [KO:K04428] [EC:2.7.11.25]

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

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

[KO:K16342] [EC:3.1.1.4]

GNRH1; progonadoliberin-1 [KO:K05252]

[KO:K05858] [EC:3.1.4.11]

ADCY1; adenylate cyclase type 1 isoform X1 [KO:K08041] [EC:4.6.1.1]

ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]

MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]

MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]

CALM3; calmodulin-3 [KO:K02183]

PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]

PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]

MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]

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

HBEGF; proheparin-binding EGF-like growth factor isoform X1 [KO:K08523]

MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]

PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]

JUN; transcription factor AP-1 [KO:K04448]

MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]

PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]

ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]

MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]

MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]

MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]

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

Cytokine-cytokine receptor interaction

Neuroactive ligand-receptor interaction

KO pathway

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