VEGF Signaling

Vascular endothelial growth factors (VEGFs) constitute a sub-family of growth factors that stimulate the growth of new blood vessels. VEGFs are important signaling proteins and initiate angiogenesis via several signalling cascades. All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (VEGFRs) on the cell surface. VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF1. After receptor dimerization and autophosphorylation, several SH2 domain-containing signal transduction molecules are activated such as PLC-γ), VRAP (VEGF Receptor-Associated Protein), Sck, and Src2.

PLC-Gamma catalyzes the hydrolysis of PIP2 (Phosphatidylinositol-4, 5-Bisphosphate), creating IP3 (Inositol Trisphosphate) and DAG (Diacylglycerol), which stimulate the release of Ca2+ from internal stores. Ca2+ release promotes NO (Nitric Oxide) production via NOS (Nitric Oxide Synthase) as well as activativation PKC (Protein Kinase-C). NO regulates hematopoiesis and modulates cell growth.Together with PKC activation via DAG, the formation of SHC-GRB2-SOS complex enables the Raf1-MEK-ERK pathway3. Cell survival signal is mainly mediated through PI3K-mediated activation of Akt/PKB (Protein Kinase-B). BAD as well as Caspase-9 can inactivate Akt/Pkb ultimately leading to apoptosis instead of cell survival. p38 pathway transduces the VEGF information concerning Actin organization via MAPKAPK2/3 (MAP Kinase Activated Protein Kinase-2/3) and phosphorylation of the F-Actin polymerization modulator, HSP27 (Heat Shock Protein-27). The activation of PTK2 and Paxillin over VEGFR2 leads to recruitment Talin and Vinculin to the focal adhesion plaque4. These Actin-anchoring proteins further support actin reorganization5.

When VEGF is overexpressed, it can contribute to disease. Cancers that can express VEGF and establish blood supply are able to grow and metastasize. Another possible result are vascular disease in the retina of the eye and other parts of the body. Drugs such as Pegaptnib, Bevacizumab, and Ranibizumab can inhibit VEGF and control or slow those diseases.


References:

  1. Matsumoto T, (2001): “VEGF receptor signal transduction”. Sci STKE, 112:re21 [PMID: 11741095]
  2. Li-Wha Wu(1999): “VRAP Is an Adaptor Protein That Binds KDR, a Receptor for Vascular Endothelial Cell Growth Factor. ” J. Biol. Chem., 275, 6059-6062 [DOI: 10.1074]
  3. Harmer SL(1997): "Shc contains two Grb2 binding sites needed for efficient formation of complexes with SOS in B lymphocytes.” Mol Cell Biol, Jul;17(7):4087-95. [PMID: 9199344]
  4. Brian P.(2002): “Src-mediated coupling of focal adhesion kinase to integrin αvβ5 in vascular endothelial growth factor signaling ” Mol Cell endocrinol, 217(1-2):67-74.. [PMID: 2173263]
  5. Ganju RK (1998): “Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells. ” J Virol., Jul;72(7):6131-7. [PMID: 9621077]


Adaptor Proteins & Growth Factors

VEGFA - VEGF

This gene is a member of the PDGF/VEGF growth factor family and encodes a protein that is often found as a disulfide linked homodimer. This protein is a glycosylated mitogen that specifically acts on endothelial cells and has various effects, including mediating increased vascular permeability, inducing angiogenesis, vasculogenesis and endothelial cell growth, promoting cell migration, and...   More...

KDR - VEGFR2

Antigens in this category:
FLT4 (Fms-Related Tyrosine Kinase 4): FLT4 antibodies FLT4 ELISA Kits FLT4 Proteins
PXN - Paxillin: PXN antibodies PXN ELISA Kits PXN Proteins
SH2D2A - SH2 Domain Protein 2A: SH2D2A antibodies   SH2D2A Proteins
SHC2 (SHC (Src Homology 2 Domain Containing) Transforming Protein 2): SHC2 antibodies SHC2 ELISA Kits SHC2 Proteins
TGFB1I1 (Transforming Growth Factor beta 1 Induced Transcript 1): TGFB1I1 antibodies TGFB1I1 ELISA Kits TGFB1I1 Proteins
PKCa - PKC alpha: PKCa antibodies PKCa ELISA Kits PKCa Proteins

GTPases & Ca2+ Cycle

Antigens in this category:
CAN - Calcineurin B: CAN antibodies    
CHP - Calcium Binding Protein P22: CHP antibodies CHP ELISA Kits CHP Proteins
CDC42 (Cell Division Cycle 42): CDC42 antibodies CDC42 ELISA Kits  
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): CDC42 antibodies CDC42 ELISA Kits CDC42 Proteins
NRAS - GTPase NRas: NRAS antibodies NRAS ELISA Kits NRAS Proteins
HRAS1 - Harvey Rat Sarcoma Virus Oncogene 1: HRAS1 antibodies HRAS1 ELISA Kits HRAS1 Proteins
NANOS3 (Nanos Homolog 3): NANOS3 antibodies   NANOS3 Proteins
NOS3 - ENOS: NOS3 antibodies NOS3 ELISA Kits NOS3 Proteins
NFAT1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 2): NFAT1 antibodies NFAT1 ELISA Kits NFAT1 Proteins
RAC1 (Ras-Related C3 Botulinum Toxin Substrate 1 (Rho Family, Small GTP Binding Protein Rac1)): RAC1 antibodies RAC1 ELISA Kits  
RAC2 (Ras-Related C3 Botulinum Toxin Substrate 2 (Rho Family, Small GTP Binding Protein Rac2)): RAC2 antibodies RAC2 ELISA Kits RAC2 Proteins
RAC3 (Ras-Related C3 Botulinum Toxin Substrate 3 (Rho Family, Small GTP Binding Protein Rac3)): RAC3 antibodies RAC3 ELISA Kits RAC3 Proteins

Phospholipases

Antigens in this category:
JMJD7-PLA2G4B (JMJD7-PLA2G4B Readthrough): JMJD7-PLA2G4B antibodies    
YWHAZ (Phospholipase A2): YWHAZ antibodies YWHAZ ELISA Kits YWHAZ Proteins
PLA2G4A - phospholipase A2, Group IVA (Cytosolic, Calcium-Dependent): PLA2G4A antibodies PLA2G4A ELISA Kits PLA2G4A Proteins
PLA2G4B (phospholipase A2, Group IVB Cytosolic): PLA2G4B antibodies   PLA2G4B Proteins
PLA2G4C (Phospholipase A2, Group IVC (Cytosolic, Calcium-Independent)): PLA2G4C antibodies   PLA2G4C Proteins
PLA2G4D (phospholipase A2, Group IVD (Cytosolic)):   PLA2G4D ELISA Kits  
PLA2G4E - Phospholipase A2, Group IVE: PLA2G4E antibodies    
PLCG2 - Phospholipase C gamma 2: PLCG2 antibodies PLCG2 ELISA Kits PLCG2 Proteins
PLCG1 - Phospholipase C gamma 1: PLCG1 antibodies PLCG1 ELISA Kits PLCG1 Proteins
PI3K - Phosphotylinosital 3 Kinase: PI3K antibodies PI3K ELISA Kits PI3K Proteins

Protein Kinases & HSPs

Antigens in this category:
HSPB1 (Heat Shock 27kDa Protein 1): HSPB1 antibodies HSPB1 ELISA Kits HSPB1 Proteins
HSP27 - Heat Shock Protein 27:   HSP27 ELISA Kits  
MAPK - Mitogen-Activated Protein Kinase: MAPK antibodies MAPK ELISA Kits  
PRKCG - PKC gamma: PRKCG antibodies PRKCG ELISA Kits PRKCG Proteins
PTK2 - FAK: PTK2 antibodies PTK2 ELISA Kits PTK2 Proteins
PTK2B (PTK2B Protein tyrosine Kinase 2 beta): PTK2B antibodies PTK2B ELISA Kits PTK2B Proteins
AKT1 - AKT: AKT1 antibodies AKT1 ELISA Kits AKT1 Proteins
AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2): AKT2 antibodies AKT2 ELISA Kits AKT2 Proteins
AKT3 (V-Akt Murine Thymoma Viral Oncogene Homolog 3 (Protein Kinase B, Gamma)): AKT3 antibodies AKT3 ELISA Kits AKT3 Proteins
HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): HRAS antibodies HRAS ELISA Kits HRAS Proteins
RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1): RAF1 antibodies RAF1 ELISA Kits RAF1 Proteins
SRC (V-Src Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog (Avian)): SRC antibodies SRC ELISA Kits SRC Proteins
PRKCB - PKC beta: PRKCB antibodies PRKCB ELISA Kits PRKCB Proteins
PKCa - PKC alpha: PKCa antibodies PKCa ELISA Kits PKCa Proteins

Protein Phosphatases

Antigens in this category:
PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): PIK3CA antibodies PIK3CA ELISA Kits PIK3CA Proteins
PIK3CG (Phosphoinositide-3-Kinase, Catalytic, gamma Polypeptide): PIK3CG antibodies PIK3CG ELISA Kits PIK3CG Proteins
PIK3R5 (Phosphoinositide-3-Kinase, Regulatory Subunit 5): PIK3R5 antibodies PIK3R5 ELISA Kits PIK3R5 Proteins
PI3KR5 (PI3KR5): PI3KR5 antibodies    
PPP3CA (Protein Phosphatase 3, Catalytic Subunit, alpha Isoform): PPP3CA antibodies PPP3CA ELISA Kits PPP3CA Proteins
PPP3CB (Protein Phosphatase 3, Catalytic Subunit, beta Isozyme): PPP3CB antibodies PPP3CB ELISA Kits PPP3CB Proteins
PPP3CC (Protein Phosphatase 3, Catalytic Subunit, gamma Isozyme): PPP3CC antibodies PPP3CC ELISA Kits PPP3CC Proteins
PPP3R1 (Protein Phosphatase 3, Regulatory Subunit B, alpha): PPP3R1 antibodies PPP3R1 ELISA Kits PPP3R1 Proteins
SPHK1 - Sphingosine Kinase 1: SPHK1 antibodies SPHK1 ELISA Kits SPHK1 Proteins
SPHK2 - Sphingosine Kinase 2: SPHK2 antibodies SPHK2 ELISA Kits SPHK2 Proteins
(pi-3 Kinase P85 beta):