VEGF165b

Vascular endothelial growth factor-A (VEGF-A) is a potent mediator of both angiogenesis and vasculogenesis in the fetus and adult. Humans express two sets of alternately spliced isoforms of 121, 145, 165, 183, 189, and 206 amino acids. VEGF165 appears to be the most abundant and potent of the angiogenic isoform set, followed by VEGF121 and VEGF189. The anti-angiogenic or "b" set of isoforms is differentially spliced to contain six alternate amino acids at the C-terminus, and are the more highly expressed isoforms in normal adult tissue. VEGF165b, like VEGF121 but unlike most angiogenic isoforms, does not bind heparins and is therefore diffusible. VEGFs bind the type I transmembrane receptor tyrosine kinases VEGFR1 (Flt1) and VEGFR2 (Flk1/KDR) on endothelial cells. Although VEGF affinity is highest for binding to Flt1, KDR appears to be the primary mediator of VEGF angiogenic activity. The affinity of VEGF165b for KDR is similar to that of VEGF165, but VEGF165b only partially activates KDR such that the kinase regulatory site Y1054 is not phosphorylated. VEGF165b also does not bind Neuropilin-1, suggesting that the functional difference between VEGF165 and VEGF165b may be due to either the lack of Neuropilin-1 co-signaling or unique downstream signaling activated by VEGF165b. Since VEGF165b may compete with angiogenic VEGFs for KDR sites, its ectopic expression in tumors has been shown to inhibit their growth.

Lyophilized samples are stable for greater than six months at -20C to -70C. Reconstituted VEGF165 should be stored in working aliquots at -20C.

164

7422

NM_001171629.1