Abstract
Vascular endothelial growth factor-A (VEGF-A) is essential for endothelial cell functions associated with angiogenesis. Signal transduction networks initiated by VEGFA/VEGFR2, the most prominent ligand-receptor complex in the VEGF system, leads to endothelial cell proliferation, migration, survival and new vessel formation involved in angiogenesis. Considering its biomedical importance, we have developed the first comprehensive map of endothelial cell-specific signaling events of VEGFA/VEGFR2 system pertaining to angiogenesis. Screening over 20,000 published research articles and following the post-translational modification (PTM) and site specificity of VEGFR2, we have documented 240 proteins and their diverse PTM-dependent reactions involved in VEGFA/VEGFR2 signal transduction. From the ligand-receptor complex, this map has been extended to the level of major transcriptionally regulated genes for which the signaling cascades leading to their transcription factors are reported. We believe that this map would serve as a novel platform for reference, integration, and representation and more significantly, the progressive analysis of dynamic features of VEGF signaling in endothelial cells including their cross-talks with other ligand-receptor systems involved in angiogenesis.
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Abbreviations
- AMPK:
-
AMP-activated protein kinase
- CDC42:
-
Cell division cycle 42
- cGMP:
-
Cyclic GMP
- COX-2:
-
Cyclooxygenase-2
- CTGF/CCN2:
-
Connective tissue growth factor
- DAG:
-
Diacyl glycerol
- Dll4:
-
Delta like-4
- EC:
-
Endothelial cells
- ECM:
-
Extracellular matrix
- EGF:
-
Epidermal growth factor
- eNOS:
-
Endothelial nitric oxide synthase
- ERK:
-
Extracellular-signal-regulated kinases
- FAK:
-
Focal adhesion kinase
- FGF:
-
Fibroblast growth factor
- FOXO:
-
Forkhead transcription factors
- FRS2:
-
Fibroblast growth factor receptor substrate 2
- FSH:
-
Follicle stimulating hormone
- HSP27:
-
Heat shock protein 27
- HSPG:
-
Heparan sulphate proteoglycan
- IP3:
-
Inositol-1,4,5-triphosphate
- JNK:
-
Janus kinase
- MKK3:
-
Mitogen activated protein kinase kinase3
- MMPs:
-
Matrix metalo proteases
- MTOR:
-
Mammalian target of rapamycin
- NCK:
-
Non-catalytic region of tyrosine kinase adaptor protein
- NRP:
-
Neuropilin
- p38MAPK:
-
p38 mitogen-activated protein kinases
- PCR:
-
Polymerase chain reaction
- PI3K:
-
Phosphatidyl inositol -3-kinase
- PIP2:
-
Phosphatidyl inositol 4, 5-diphosphate
- PKB:
-
Protein kinase B
- PKC:
-
Protein kinase C
- PLC-γ:
-
Phospholipase C-γ
- PlGF:
-
Placental growth factor
- PTM:
-
Post-translational modification
- RAC:
-
Ras-related C3 botulinum toxin substrate
- SAPK2/p38:
-
Stress-activated protein kinase 2/p38
- SCK:
-
Shc-related adaptor protein
- SHB:
-
SH2 domain containing adaptor protein B
- siRNA:
-
Small interfering RNA
- SRC:
-
SRC proto-oncogene
- t-SNARE:
-
t-soluble N-ethylmaleimide attachment protein receptor
- VEGF-A:
-
Vascular endothelial growth factor-A
- VEGFR1:
-
Vascular endothelial growth factor receptor 1
- VEGFR2:
-
Vascular endothelial growth factor receptor 2
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Acknowledgment
Financial assistance from Kerala State Council for Science Technology and Environment, Thiruvananthapuram, is gratefully acknowledged.
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Table I
List of total proteins (with gene name and gene ID) in the VEGFA/VEGFR2 pathway map (XLS 77 kb)
Table II
Classification of VEGF AA-VEGF AR2 signaling molecules based on their role in cellular function (XLS 33.5 kb)
Table III
Classification of molecules based on cellular functions (DOC 111 kb)
Table IV
List of molecular associations, catalysis, transport, VEGF regulated phosphosites and indirect interactions in the VEGFA/VEGFR2 pathway map (XLS 80 kb)
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Abhinand, C.S., Raju, R., Soumya, S.J. et al. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J. Cell Commun. Signal. 10, 347–354 (2016). https://doi.org/10.1007/s12079-016-0352-8
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DOI: https://doi.org/10.1007/s12079-016-0352-8