VEGFR and Type-V RTK Activation and Signaling

被引：102

作者：

Shibuya, Masabumi ^{[1
,2
]}

机构：

[1] Jobu Univ, Isesaki, Gunma 3728588, Japan

[2] Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan

来源：

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY | 2013年 / 5卷 / 10期

关键词：

ENDOTHELIAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; TUMOR ANGIOGENESIS; CELL GROWTH; BONE-MARROW; IN-VIVO; VASCULAR-PERMEABILITY; EXTRACELLULAR DOMAIN; SOLUBLE VEGFR-1; TRANSGENIC MICE;

D O I：

10.1101/cshperspect.a009092

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Vascular endothelial growth factor receptors (VEGFRs) in vertebrates play essential roles in the regulation of angiogenesis and lymphangiogenesis. VEGFRs belong to the receptor-type tyrosine kinase (RTK) supergene family. They consist of a ligand-binding region with seven immunoglobulin (7 Ig) -like domains, a trans-membrane (TM) domain, and a tyrosine kinase (TK) domain with a long kinase insert (KI) (also known as a type-V RTK). Structurally, VEGFRs are distantly related to the members of the M-colony stimulating factor receptor/platelet-derived growth factor receptor (CSFR)/(PDGFR) family, which have five immunoglobulin (5 Ig)-like domains. However, signal transduction in VEGFRs significantly differs from that in M-CSFR/PDGFRs. VEGFR2, the major signal transducer for angiogenesis, preferentially uses the phospholipase C gamma-protein kinase C (PLC-gamma-PKC)-MAPK pathway, whereas M-CSFR/PDGFRs use the PI3 kinase-Ras-MAPK pathway for cell proliferation. In phylogenetic development, the VEGFR-like receptor in nonvertebrates appears to be the ancestor of the 7 Ig- and 5 Ig-RTK families because most nonvertebrates have only a single 7 Ig-RTK gene. In mammals, VEGFRs are deeply involved in pathological angiogenesis, including cancer and inflammation. Thus, an efficient inhibitor targeting VEGFRs could be useful in suppressing various diseases.

引用

页数：13

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