Characterization of novel VEGF (vascular endothelial growth factor)-C splicing isoforms from mouse.
VEGF (vascular endothelial growth factor)-C is a major growth factor implicated in various physiological processes, such as angiogenesis and lymphangiogenesis. In the present paper, we report the identification of three short VEGF-C splicing isoforms (VEGF-C62, VEGF-C129 and VEGF-C184) from immortalized mouse kidney PTECs (proximal tubular epithelial cells). Semi-quantitative RT (reverse transcription)-PCR analysis showed these isoforms were universally expressed to varying degrees in different tissues with high expression levels in the kidney. In immortalized PTECs and podocytes, VEGF-C62 can activate phosphorylation of FAK (focal adhesion kinase) and promote cell adhesion to substratum. Cell survival was also increased by VEGF-C62 treatment in the absence of serum. VEGF-C62 can also reduce cell proliferation in PTECs and podocytes. Nucleolin was one of the proteins that associated with VEGF-C62 in pull-down assays using GST (glutathione transferase) fusion proteins as bait, indicating different protein binding requirements for VEGF-C62 compared with VEGF-C. In conclusion, these newly identified VEGF-C isoforms represent a new class of proteins, which are potentially involved in epithelial cell adhesion and proliferation through novel receptor pathways.
Wang
Zhen-Guo
ZG
Department of Medicine, Section of Nephrology, The University of Chicago, Chicago, IL 60637, USA. zwang1@medicine.bsd.uchicago.edu
Puri
Tipu S
TS
Quigg
Richard J
RJ
D000818:Animals; D002448:Cell Adhesion; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D042582:Vascular Endothelial Growth Factor C