tailieunhanh - Báo cáo khoa học: The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1

Vascular endothelial growth factor (VEGF) family members play impor-tant roles in embryonic development and angiogenesis during wound healing and in pathological conditions such as tumor formation. Parapox-viruses express a new member of the VEGF family which is a functional mitogen that specifically activates VEGF receptor (VEGFR)-2 but not VEGFR-1. | ỊFEBS Journal The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1 Marie K. Inder Lyn M. Wise Stephen B. Fleming and Andrew A. Mercer Department of Microbiology and Immunology University of Otago Dunedin New Zealand Keywords Orf virus Parapoxvirus vascular endothelial growth factor VEGF-E vascular endothelial growth factor receptor Correspondence L. M. Wise Virus Research Unit Department of Microbiology and Immunology University of Otago PO Box 56 Dunedin New Zealand Fax 64 3 479 7744 Tel 64 3 479 7723 E-mail Received 12 August 2007 revised 24 October 2007 accepted 12 November 2007 Vascular endothelial growth factor VEGF family members play important roles in embryonic development and angiogenesis during wound healing and in pathological conditions such as tumor formation. Parapoxviruses express a new member of the VEGF family which is a functional mitogen that specifically activates VEGF receptor VEGFR -2 but not VEGFR-1. In this study we show that deletion from the viral VEGF of a unique C-terminal region increases both VEGFR-1 binding and VEGFR-1-mediated monocyte migration. Enzymatic removal of O-linked glycosylation from the C-terminus also increased VEGFR-1 binding and migration of THP-1 monocytes indicating that both the C-terminal residues and O-linked sugars contribute to blocking viral VEGF binding to VEGFR-1. The data suggest that conservation of the C-terminal residues throughout the viral VEGF subfamily may represent a means of reducing the immunostimulatory activities associated with VEGFR-1 activation while maintaining the ability to induce angiogenesis via VEGFR-2. doi Members of the vascular endothelial growth factor VEGF family of molecules have emerged as major regulators of new blood vessel formation during vascu-logenesis and angiogenesis 1-3 . These proteins have critical roles during embryogenesis and in normal adult tissues .