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 (the 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 (Vascular Endothelial Growth Factor A):

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...   更多...

KDR - VEGFR2

此分类里的别的抗原:
FLT4 (Fms-Related Tyrosine Kinase 4): FLT4 抗体 FLT4 ELISA试剂盒 FLT4 蛋白
PXN - Paxillin: PXN 抗体 PXN ELISA试剂盒 PXN 蛋白
SH2D2A - SH2 Domain Protein 2A: SH2D2A 抗体   SH2D2A 蛋白
SHC2 (SHC (Src Homology 2 Domain Containing) Transforming Protein 2): SHC2 抗体   SHC2 蛋白
TGFB1I1 (Transforming Growth Factor beta 1 Induced Transcript 1): TGFB1I1 抗体   TGFB1I1 蛋白
PKCa - PKC alpha: PKCa 抗体 PKCa ELISA试剂盒 PKCa 蛋白

GTPases & Ca2+ Cycle

此分类里的别的抗原:
CAN - Calcineurin B: CAN 抗体    
CHP - Calcium Binding Protein P22: CHP 抗体   CHP 蛋白
CDC42 (Cell Division Cycle 42): CDC42 抗体 CDC42 ELISA试剂盒  
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): CDC42 抗体 CDC42 ELISA试剂盒 CDC42 蛋白
NRAS - GTPase NRas: NRAS 抗体 NRAS ELISA试剂盒 NRAS 蛋白
HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): HRAS 抗体 HRAS ELISA试剂盒 HRAS 蛋白
NANOS3 (Nanos Homolog 3): NANOS3 抗体    
NOS3 - ENOS: NOS3 抗体 NOS3 ELISA试剂盒 NOS3 蛋白
NFAT1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 2): NFAT1 抗体 NFAT1 ELISA试剂盒 NFAT1 蛋白
- RAC1: 抗体 ELISA试剂盒  
RAC2 (Ras-Related C3 Botulinum Toxin Substrate 2 (Rho Family, Small GTP Binding Protein Rac2)): RAC2 抗体   RAC2 蛋白
RAC3 (Ras-Related C3 Botulinum Toxin Substrate 3 (Rho Family, Small GTP Binding Protein Rac3)): RAC3 抗体   RAC3 蛋白

Phospholipases

此分类里的别的抗原:
JMJD7-PLA2G4B (JMJD7-PLA2G4B Readthrough): JMJD7-PLA2G4B 抗体    
YWHAZ (Phospholipase A2): YWHAZ 抗体 YWHAZ ELISA试剂盒 YWHAZ 蛋白
PLA2G4A - phospholipase A2, Group IVA (Cytosolic, Calcium-Dependent): PLA2G4A 抗体 PLA2G4A ELISA试剂盒 PLA2G4A 蛋白
PLA2G4B (phospholipase A2, Group IVB Cytosolic): PLA2G4B 抗体   PLA2G4B 蛋白
PLA2G4C (Phospholipase A2, Group IVC (Cytosolic, Calcium-Independent)): PLA2G4C 抗体   PLA2G4C 蛋白
PLA2G4D (phospholipase A2, Group IVD (Cytosolic)):   PLA2G4D ELISA试剂盒  
PLA2G4E - Phospholipase A2, Group IVE: PLA2G4E 抗体    
PLCG2 - Phospholipase C gamma 2: PLCG2 抗体 PLCG2 ELISA试剂盒 PLCG2 蛋白
PLCG1 - Phospholipase C gamma 1: PLCG1 抗体 PLCG1 ELISA试剂盒 PLCG1 蛋白
(PI3 Kinase P85 alpha):      

Protein Kinases & HSPs

此分类里的别的抗原:
HSPB1 (Heat Shock 27kDa Protein 1): HSPB1 抗体 HSPB1 ELISA试剂盒 HSPB1 蛋白
HSP27 - Heat Shock Protein 27:   HSP27 ELISA试剂盒  
MAPK - Mitogen-Activated Protein Kinase: MAPK 抗体 MAPK ELISA试剂盒  
PRKCG - PKC gamma: PRKCG 抗体 PRKCG ELISA试剂盒 PRKCG 蛋白
PTK2 - FAK: PTK2 抗体 PTK2 ELISA试剂盒 PTK2 蛋白
PTK2B (PTK2B Protein tyrosine Kinase 2 beta): PTK2B 抗体 PTK2B ELISA试剂盒 PTK2B 蛋白
AKT1 - AKT: AKT1 抗体 AKT1 ELISA试剂盒 AKT1 蛋白
AKT2 (V-Akt Murine Thymoma Viral Oncogene Homolog 2): AKT2 抗体 AKT2 ELISA试剂盒 AKT2 蛋白
AKT3 (V-Akt Murine Thymoma Viral Oncogene Homolog 3 (Protein Kinase B, Gamma)): AKT3 抗体 AKT3 ELISA试剂盒 AKT3 蛋白
HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): HRAS 抗体 HRAS ELISA试剂盒 HRAS 蛋白
RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1): RAF1 抗体 RAF1 ELISA试剂盒 RAF1 蛋白
SRC (V-Src Sarcoma (Schmidt-Ruppin A-2) Viral Oncogene Homolog (Avian)): SRC 抗体 SRC ELISA试剂盒 SRC 蛋白
PRKCB - PKC beta: PRKCB 抗体 PRKCB ELISA试剂盒 PRKCB 蛋白
PKCa - PKC alpha: PKCa 抗体 PKCa ELISA试剂盒 PKCa 蛋白

Protein Phosphatases

此分类里的别的抗原:
PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): PIK3CA 抗体 PIK3CA ELISA试剂盒 PIK3CA 蛋白
PIK3CG (Phosphoinositide-3-Kinase, Catalytic, gamma Polypeptide): PIK3CG 抗体   PIK3CG 蛋白
PIK3R5 (Phosphoinositide-3-Kinase, Regulatory Subunit 5): PIK3R5 抗体   PIK3R5 蛋白
PPP3CA (Protein Phosphatase 3, Catalytic Subunit, alpha Isoform): PPP3CA 抗体 PPP3CA ELISA试剂盒 PPP3CA 蛋白
PPP3CB (Protein Phosphatase 3, Catalytic Subunit, beta Isozyme): PPP3CB 抗体   PPP3CB 蛋白
PPP3CC (Protein Phosphatase 3, Catalytic Subunit, gamma Isozyme): PPP3CC 抗体   PPP3CC 蛋白
PPP3R1 (Protein Phosphatase 3, Regulatory Subunit B, alpha): PPP3R1 抗体 PPP3R1 ELISA试剂盒 PPP3R1 蛋白
SPHK1 - Sphingosine Kinase 1: SPHK1 抗体 SPHK1 ELISA试剂盒 SPHK1 蛋白
SPHK2 - Sphingosine Kinase 2: SPHK2 抗体 SPHK2 ELISA试剂盒 SPHK2 蛋白
(pi-3 Kinase P85 beta):