Article

Signal transduction by vascular endothelial growth factor receptors

Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Biochemical Journal (Impact Factor: 4.78). 07/2011; 437(2):169-83. DOI: 10.1042/BJ20110301
Source: PubMed

ABSTRACT VEGFs (vascular endothelial growth factors) control vascular development during embryogenesis and the function of blood vessels and lymphatic vessels in the adult. There are five related mammalian ligands, which act through three receptor tyrosine kinases. Signalling is modulated through neuropilins, which act as VEGF co-receptors. Heparan sulfate and integrins are also important modulators of VEGF signalling. Therapeutic agents that interfere with VEGF signalling have been developed with the aim of decreasing angiogenesis in diseases that involve tissue growth and inflammation, such as cancer. The present review will outline the current understanding and consequent biology of VEGF receptor signalling.

0 Followers
 · 
142 Views
 · 
0 Downloads
    • "[30] Upon binding of VEGF, phosphorylation of tyrosine residues on VEGFR stimulates activation of protein kinase B, which inhibits apoptosis, and of the mitogen-activated protein kinase (MAPK) pathway, which induces cell proliferation. [31] Thus, VEGFR2 play an important role in wound healing particularly in angiogenesis. [7] Hence to understand the mechanisms and effects of lactate and VEGF at molecular level, VEGFR2 expression was quantified by q-PCR. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Growth factor therapies to induce angiogenesis and thereby enhance the blood perfusion, hold tremendous potential to address the shortcomings of current impaired/diabetic wound care modalities. Vascular endothelial growth factor stimulates (VEGF) wound healing via multiple mechanisms. Poly(lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. Hence, we hypothesized that the administration of VEGF encapsulated in PLGA nanoparticles (PLGA-VEGF NP) would promote fast healing due to the sustained and combined effects of VEGF and lactate. In a splinted mouse full thickness excision model, compared with untreated, VEGF and PLGA NP, PLGA-VEGF NP treated wounds showed significant granulation tissue formation with higher collagen content, re-epithelialization and angiogenesis. The cellular and molecular studies revealed that PLGA-VEGF NP enhanced the proliferation and migration of keratinocytes and upregulated the expression of VEGFR2 at mRNA level. We demonstrated the combined effects of lactate and VEGF for active healing of non-diabetic and diabetic wounds. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine: nanotechnology, biology, and medicine 07/2015; DOI:10.1016/j.nano.2015.07.006 · 5.98 Impact Factor
    • "VEGF also binds to non-tyrosine-kinase receptors of the neuropilinfamily , NRP1 and NRP2, which act as co-receptors of the other VEGFR [1]. After VEGF binding, tyrosine-kinase receptors dimerize, followed by conformational changes that finally lead to the activation of a downstream signaling cascade [1]. For example, phosphorylation of the tyrosineresidue 1214 in the VEGFR-2 is known to activate signaling cascades for actin reorganization in endothelial cells [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Over the last decade, our understanding of the vascular endothelial growth factor (VEGF) has rapidly increased, becoming the focus of many investigations the world over. Besides its classical role in the vascular system, VEGF was also identified as a factor affecting the nervous system. One structure that responds to VEGF-signaling is the axonal growth cone, the correct behavior of which is essential for the development of a properly working neuronal network. It navigates growing axons to their final destination and helps to create proper synapses at predetermined locations. Recent data concerning the impact of VEGF on the actin cytoskeleton of neuronal growth cones are discussed and new findings of VEGF-signaling in regard to actin dynamics are specified. Overall, we describe the role of VEGF regulation of cofilin and the Arp2/3-complex in axonal growth cones.
    Current neurovascular research 06/2015; 12(999). DOI:10.2174/1567202612666150603141144 · 2.74 Impact Factor
  • Source
    • "Angiogenesis is important in tumor growth and metastasis . It is primarily driven by VEGF-A (Vascular Endothelial Growth Factor) [124], acting through binding on VEGF Re- ceptor-2 (VEGFR-2) [125], the latter expressed on endothelial cells. VEGFR-2 engagement by VEGF results in endothelial cell proliferation, migration and motility [126], while VEGFR-1 is thought to act as a decoy receptor. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast carcinoma is currently considered as a group of diseases, differing not only in histopathologic phenotype, as indicated by histologic type and grade, but also in their protein, genetic and epigenetic molecular profile. The standard of care indicates that the core information for patient management includes data on Estrogen Receptor (ER), Progesterone Receptor (PgR) and Human Epidermal Growth Factor Receptor 2 (HER2), while there is an emerging role for the proliferation marker Ki67. These indices can be provided even in low resource settings and are indispensable for prognostication and therapeutic patient management. With the progress in molecular and translational research, there is a growing body of information on the molecular subtypes of breast carcinoma and their significance, and multigene signature assays are used to dictate prognosis and guide therapeutics in high resource settings. In addition, several cellular pathways involved in tumor growth and spread are dissected and targeted in clinical trials. Among these are the p53, RB, PI3K/Akt/mTOR and Ras/MAPK pathways, alterations associated with genetic instability and epigenetic alterations including histone methylation and acetylation, DNA methylation and microRNAs expression. The tumor immune microenvironment, including the tumor infiltrating lymphocytes (TILs) is attracting significant research interest. This review summarizes the mechanisms of function of the above factors in breast tumorigenesis with emphasis on their prognostic and predictive value and their use as therapeutic targets.
    Current molecular pharmacology 01/2015; 7(1):4-21. DOI:10.2174/187446720701150105170830
Show more