Abstract
Oncogenic mutations of G proteins and G protein-coupled receptors (GPCRs) have been identified in various endocrine tumors for almost 20 years. Chronic inflammation contributes to tumorigenesis by the induction of cytokine and chemokine production and leukocyte infiltration. Many inflammatory mediators and chemoattractants elicit their effects by stimulating specific GPCRs. The subsequent activation of various G proteins often results in the modulation of transcription factors via complex signaling networks. Human herpesviruses can even resort to hijacking such control by making their own constitutive GPCRs that eventually lead to the development of Kaposi’s sarcoma. Increasing evidence indicates that inflammation-related transcription factors such as STAT3 and NFκB are common effectors of converging streams of G protein signals, which further signifies the importance of G protein-mediated regulations of inflammatory actions and tumorigenesis. This chapter aims to review the regulations of transcription factors mediated by G proteins and the biological relevance of cross-communications between different signaling cascades.
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Abbreviations
- A1R, A2AR, A2BR, A3R:
-
Types 1, 2A, 2B and 3 adenosine receptors
- Akt:
-
Protein kinase B
- AP-1:
-
Activator protein-1
- AT1R:
-
Type 1 angiotension II receptor
- ATF-2:
-
Activating transcription factor-2
- ASMC:
-
Airway smooth muscle cells
- Bax:
-
Bcl-2-associated X protein
- Bcl-2:
-
B-cell CLL/lymphoma 2
- bFGF:
-
Basic fibroblast growth factor
- BK1R, BK2R:
-
Types 1 and 2 bradykinin receptors
- BLT1, BLT2 :
-
Types 1 and 2 leukotriene B4 receptors
- C5a:
-
Complement 5a
- cAMP:
-
Cyclic AMP
- CaM:
-
Calmodulin
- CaMKII:
-
Calmodulin kinase II
- CBP:
-
CREB-binding protein
- CCR:
-
CC chemokine receptor
- C/EBPδ:
-
CCAAT/enhancer binding protein δ
- CHO:
-
Chinese hamster ovary cells
- COX-2:
-
Cyclooxygenase-2
- CREB:
-
Cyclic AMP-responsive element binding protein
- c-Src:
-
Cellular-sarcoma
- CXCR:
-
CXC chemokine receptor
- DAG:
-
Diacylglycerol
- Egr-3:
-
Early growth response-3
- EGF:
-
Epidermal growth factor
- EP4:
-
Prostaglandin E4 receptor
- Epac:
-
Exchange proteins directly activated by cAMP
- EPRAP:
-
EP4 receptor-associated protein
- ERK:
-
Extracellular signal-regulated kinase
- fMLP:
-
N-formyl-methionyl-leucyl-phenylalaine
- G-CSF:
-
Granulocyte colony-stimulating factor
- GM-CSF:
-
Granulocyte/macrophage colony-stimulating factor
- G protein:
-
Heterotrimeric guanine nucleotide binding regulatory protein
- GPCR:
-
G protein-coupled receptor
- GRPR:
-
Gastrin-releasing peptide-preferring receptor
- H1R, H2R:
-
Types 1 and 2 histamine receptors
- HCMV:
-
Human cytomegalovirus
- hBD-3:
-
Human β-defensin-3
- HEK293:
-
Human embryonic kidney 293 cells
- HEL:
-
Human erythroleukemia cells
- hIP:
-
Human prostacyclin receptor
- HUVEC:
-
Human umbilical vein endothelial cells
- ICAM-1:
-
Intercellular cell adhesion molecule-1
- IFN-γ:
-
Interferon-γ
- IκB:
-
Inhibitor of κB
- IKK:
-
Inhibitor of κB kinase
- IL:
-
Interleukin
- iNOS:
-
Inducible nitric oxide synthase
- IP3 :
-
Inositol trisphosphate
- Jak:
-
Janus kinase
- JNK:
-
c-Jun N-terminal kinase
- KSHV-GPCR:
-
Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
- LHSCC:
-
Laryngeal and hypopharyngeal squamous cell carcinomas
- LPA:
-
Lysophosphatidic acid
- LPS:
-
Lipopolysaccharide
- mAKAP:
-
Muscle A kinase-anchoring protein
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemotactic protein-1
- M-CSF:
-
Macrophage-colony stimulating factor
- Mcl-1:
-
Myeloid cell leukemia sequence 1
- MEK1/2:
-
Mitogen-activated protein kinase kinase 1/2
- MIP-1α:
-
Macrophage inflammatory protein-1α
- MIP-1β:
-
Macrophage inflammatory protein-1β
- MMP:
-
Matrix metallopeptidase
- NFAT:
-
Nuclear factor of activated T-cells
- NFκB:
-
Nuclear factor κB
- NPC:
-
Nasopharyngeal carcinoma
- p38:
-
p38 mitogen-activated protein kinase
- PAF:
-
Platelet-activating factor
- PAI-1:
-
Plasminogen activator inhibitor-1
- PAR:
-
Protease-activated receptor
- PDK-1:
-
3′-phosphoinositide-dependent protein kinase-1
- PGE2:
-
Prostanglandin E2
- PI3K:
-
Phosphatidylinositol 3-kinase
- PKA:
-
Protein kinase A
- PKC:
-
Protein kinase C
- PIP2:
-
Phosphatidylinositol bisphosphate
- PLC:
-
Phospholipase C
- PPAR:
-
Peroxisome proliferator-activated receptor
- ROS:
-
Reactive oxygen species
- RyR2:
-
Ryanodine receptor 2
- SST2R, SST4R:
-
Types 2 and 4 somatostatin receptors
- STAT:
-
Signal transducer and activator of transcription
- Tac1:
-
Tachykinin 1
- TIMP-1:
-
Tissue inhibitor of metalloprotease-1
- TNF-α:
-
Tumor necrosis factor-α
- TRAIL:
-
TNF-related apoptosis-inducing ligand
- TXA2 :
-
Thromboxane A2 receptor
- Tyk2:
-
Tyrosine kinase 2
- US28:
-
Viral chemokine receptor US28
- VCAM-1:
-
Vascular cell adhesion molecule-1
- VEGF:
-
Vascular endothelial growth factor
- VSMC:
-
Vascular smooth muscle cells.
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Acknowledgements
Studies by the authors are supported in part by the Hong Kong Jockey Club, Research Grant Council (HKUST 644306, 643306 and 663108) and University Grant Council of Hong Kong (AoE/B-15/01) to YHW.
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Yeung, W.W.S., Ho, M.K.C., Wong, Y.H. (2010). Functional Impacts of Signal Integration: Regulation of Inflammation-Related Transcription Factors by Heterotrimeric G Proteins. In: Reichle, A. (eds) From Molecular to Modular Tumor Therapy. The Tumor Microenvironment, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9531-2_9
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