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Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis

Stevens, Megan ; Oltean, Sebastian

Cells (Basel, Switzerland), 2019-03, Vol.8 (4), p.288 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis
Autor: Stevens, Megan ; Oltean, Sebastian
Assuntos: Alternative splicing ; Alternative Splicing - genetics ; Amino acids ; Angiogenesis ; Animals ; Binding sites ; Drug development ; Gene expression ; Humans ; Hypoxia ; Immunoglobulins ; Isoforms ; Kinases ; Ligands ; mRNA ; Neovascularization, Physiologic - genetics ; Permeability ; Phosphorylation ; Physiology ; Protein-tyrosine kinase receptors ; Proteins ; Receptor mechanisms ; Receptors, Vascular Endothelial Growth Factor - genetics ; Retention ; Review ; Signal Transduction ; tyrosine kinase ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular endothelial growth factor receptors ; VEGF ; VEGFR
É parte de: Cells (Basel, Switzerland), 2019-03, Vol.8 (4), p.288
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Descrição: Vascular endothelial growth factor A (VEGF-A) signaling is essential for physiological and pathological angiogenesis. Alternative splicing of the VEGF-A pre-mRNA gives rise to a pro-angiogenic family of isoforms with a differing number of amino acids (VEGF-A a), as well as a family of isoforms with anti-angiogenic properties (VEGF-A b). The biological functions of VEGF-A proteins are mediated by a family of cognate protein tyrosine kinase receptors, known as the VEGF receptors (VEGFRs). VEGF-A binds to both VEGFR-1, largely suggested to function as a decoy receptor, and VEGFR-2, the predominant signaling receptor. Both VEGFR-1 and VEGFR-2 can also be alternatively spliced to generate soluble isoforms (sVEGFR-1/sVEGFR-2). The disruption of the splicing of just one of these genes can result in changes to the entire VEGF-A/VEGFR signaling axis, such as the increase in VEGF-A a relative to VEGF-A b resulting in increased VEGFR-2 signaling and aberrant angiogenesis in cancer. Research into this signaling axis has recently focused on manipulating the splicing of these genes as a potential therapeutic avenue in disease. Therefore, further research into understanding the mechanisms by which the splicing of VEGF-A/VEGFR-1/VEGFR-2 is regulated will help in the development of drugs aimed at manipulating splicing or inhibiting specific splice isoforms in a therapeutic manner.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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Modulation of Receptor Tyrosine Kinase Activity through Alternative Splicing of Ligands and Receptors in the VEGF-A/VEGFR Axis

Stevens, Megan ; Oltean, Sebastian

Switzerland: MDPI AG

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