Table 1

GPCR-mediated activation of signalling pathways leading to cell cycle modulation


Intracellular Pathway
Cell Cycle Effect
References

GPCR



Gi/o-coupled



     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



     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



     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,


     Vasopressin V1A
↑PKD
↑Proliferation
[58]

↑Ca2+/PI3K/PKC/ERK
↑G1-S phase
[105]

↑EGFR/Pyk2/Src/ERK/PI3K
↑Proliferation
[106]
G12/13-coupled



     Lysophosphatidic acid LPA

↑DNA synthesis, ↑Proliferation
[20]

↑EGFR/Rho/ROCK
↑Cyclins A/D1, ↑p21Cip1, ↓p27Kip1
[43,45]

↑JNK
↑Cyclin A
[20,54]

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