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GPCR-mediated activation of signalling pathways leading to cell cycle modulation |
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| Intracellular Pathway |
Cell Cycle Effect |
References |
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| GPCR |
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| Gi/o-coupled |
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| α1-adrenergic |
↑DNA synthesis |
[15] |
|
| ↑Src/C3G/Rap-1/B-Raf/ERK |
↑Proliferation |
[77] |
|
| Adenosine A3 |
↑PI3K/Akt/↓ERK |
↓Proliferation |
[98] |
| CXCR1/2 |
↑MMP/EGFR/ERK |
↑Proliferation |
[40] |
| CXCR3 |
↑ERK, ↑p38 |
↑DNA synthesis |
[99] |
| CXCR4 |
↑Pyk2/PI3K/ERK |
↑DNA synthesis |
[71] |
| Dopamine D2 |
↑PKC/NF-κB |
↑p21Cip1, ↑p27Kip1 |
[60] |
| ↑Src/C3G/Rap-1/B-Raf/ERK |
↑Proliferation |
[77] |
|
| Dopamine D4 |
↑Src/SHC/Ras/ERK |
↑DNA synthesis |
[78] |
| Sphingosine 1-phosphate EDG-1 |
↑p70rsk |
↑Cyclin D1 |
[96] |
| ↑PDGFβ/ERK |
↑Proliferation |
[100] |
|
| κ-opioid |
↑PLC/PKC/Ras/ERK |
↑DNA synthesis |
[16] |
| Lysophosphatidic acid LPA |
↑DNA synthesis |
[17] |
|
| Melatonin MT1 |
↓ERα/glucocorticoid receptor |
↓Cyclin D1 |
[12, 13] |
| Serotonin 5HT1E |
↑Src/C3G/Rap-1/B-Raf/ERK |
↑Proliferation |
[77] |
| Somatostatin SST1/4/5 |
↑ERK |
↑p21Cip1, ↑p27Kip1 |
[50] |
| Somatostatin SST2 |
↑PI3K/Ras/Rap-1/B-Raf/ERK |
↑p27Kip1 |
[90] |
| Somatostatin SST2a |
↑p38 |
↑p21Cip1 |
[91] |
| Somatostatin SST2b |
↑PI3K/p70rsk/Akt |
↑Proliferation |
[91] |
| Gs-coupled |
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| Dopamine D1 |
↑PLCβ/↓Raf-1 |
↓Cyclin D1/↑p27Kip1 |
[101] |
| Glucagon-like peptide GLP-1 |
EGFR/PI3K |
↑Proliferation |
[42] |
| Glucagon-like peptide GLP-2 |
↑DNA synthesis |
[18] |
|
| GPR30 |
↑PKA/CREB |
↑Cyclin D2/CDK4-6 complex formation |
[27, 28] |
| Lysophosphatidic acid LPA |
↑Proliferation |
[19] |
|
| Melanocortin MC5 |
↑JAK/STAT |
↑Proliferation |
[82] |
| Parathyroid PTH |
↑cAMP/PKA |
↑p27Kip1 |
[7, 22] |
| ↑cAMP/Epac/Rap-1/B-Raf/ERK |
↑Proliferation |
[51] |
|
| ↑cAMP/↑PKA/↓Raf-1 |
↓Proliferation |
[51] |
|
| ↑MKP-1/↓ERK |
↓Cyclin D1, ↑p21Cip1 |
[52] |
|
| Thyroid stimulating hormone TSH |
↑cAMP/CREB/c-Fos |
↑DNA synthesis, ↑Cyclins D1/E |
[14, 23-25] |
| ↑PKA/Ras/PI3K |
↑DNA synthesis |
[102] |
|
| Gq-coupled |
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| α1B-adrenergic |
↑PKC/Raf-1/ERK |
↑Proliferation |
[34] |
| ↑JNK, ↑p38 |
↓Proliferation |
[55] |
|
| ↑Src/Dbs/cdc42/MKK4/JNK |
↓Proliferation |
[76] |
|
| ↑Ras/Rac/JAK/STAT |
↑Proliferation |
[81] |
|
| Angiotensin II |
↑MMP/EGFR/ERK |
↑Cyclin D1 |
[39] |
| ↑Ras/ERK/c-Fos/c-Jun |
↑Cyclin D1, ↑pRB phosphorylation |
[48] |
|
| ↑p125FAK/Rac1/JNK |
↑Proliferation |
[67] |
|
| Bombesin |
↑MMP/EGFR/PI3K |
↑Cyclins D1/E |
[41] |
| ↑PKD |
↑Proliferation |
[58] |
|
| Bradykinin |
↑MMP/EGFR/PI3K |
↑Cyclins D1/E |
[41] |
| Endothelin |
↑MMP/EGFR/ERK |
↑DNA synthesis |
[39] |
| ↑PLCβ/Ca2+/Src/ERK |
↑Proliferation |
[74] |
|
| ↑Src/Rho/p125FAK/paxillin |
↑DNA synthesis |
[70] |
|
| ↑Pyk2/ERK |
↑DNA synthesis |
[70] |
|
| Gastrin-activated CCK2 |
↑Rho/integrin/p125FAK/paxillin |
↑Proliferation |
[68,69] |
| ↑PKC/Src/p38 |
↑Proliferation |
[75] |
|
| ↑JAK/STAT |
↑Proliferation |
[80] |
|
| Lysophosphatidic acid LPA |
↑MMP/EGFR/ERK |
↑cyclin D1 |
[39] |
| Muscarinic M1 |
↑PKC/Raf-1/ERK |
↑Proliferation |
[34] |
| Muscarinic M3 |
↑JNK/c-Jun/SP-1 |
↓DNA synthesis, ↑p21Cip1/CDK2, ↓pRb phosphorylation |
[56] |
| Muscarinic M5 |
↑Ras/Rac/JAK/STAT |
↑Proliferation |
[81] |
| Muscarinic subtypes |
↑Src/ERK/CREB |
↑DNA synthesis |
[103] |
| Platelet-Activating Factor receptor |
↑MMP/EGFR/ERK |
↑Proliferation |
[104] |
| Purinergic P2Y2/4 |
↑PKC/Raf/MAPK |
↑DNA synthesis |
[49] |
| Substance P (NK-1) |
↑Src/PKCδ/ERK |
↑Proliferation |
[72] |
| Thrombin |
↑MMP/EGFR/ERK |
↑DNA synthesis |
[39] |
| ↑RhoA/PI3K/Akt |
↓p27Kip1, ↑Cyclin D1/CDK4 |
[92-94] |
|
| ↑ERK |
↑CDK2 nuclear translocation |
[95] |
|
| ↑PI3K/Akt, |
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| Vasopressin V1A |
↑PKD |
↑Proliferation |
[58] |
| ↑Ca2+/PI3K/PKC/ERK |
↑G1-S phase |
[105] |
|
| ↑EGFR/Pyk2/Src/ERK/PI3K |
↑Proliferation |
[106] |
|
| G12/13-coupled |
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| Lysophosphatidic acid LPA |
↑DNA synthesis, ↑Proliferation |
[20] |
|
| ↑EGFR/Rho/ROCK |
↑Cyclins A/D1, ↑p21Cip1, ↓p27Kip1 |
[43,45] |
|
| ↑JNK |
↑Cyclin A |
[20,54] |
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A selection of examples is presented that demonstrate the involvement of GPCR-mediated intracellular signalling pathways in the regulation of cell cycle progression. ↑, indicates an increase in protein levels or activity; ↓, indicates a decrease in protein levels or activity. | |||
New and Wong Journal of Molecular Signaling 2007 2:2 doi:10.1186/1750-2187-2-2 |
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