Protein tyrosine kinases expressed in glomeruli and cultured glomerular cells: Flt-1 and VEGF expression in renal mesangial cells.

Protein tyrosine kinases play an important role in cellular proliferation and differentiation of various cell types. To identify potential tyrosine kinases involved in glomerular functions we have utilized the polymerase chain reaction (PCR) and degenerate oligonucleotides for isolation of such genes from isolated glomeruli, cultured mesangial cell, and glomerular endothelial cells. Sequence analysis of PCR-amplified cDNAs resulted in the isolation of 24 tyrosine kinases. Here we describe for the first time the constitutive expression of 15 tyrosine kinases, tyro-1, tyro-4, tyro-6, hyk, Ptk-3, Ryk, tie, yes, lyn, tec, Jak1, Jak2, Jak3, c-abl, and flk, in renal glomeruli. In addition, Flt-1, an endothelial cell-specific receptor for vascular endothelial growth factor (VEGF), is expressed in renal mesangial cells and its gene expression is up-regulated upon the stimulation of platelet-derived growth factor (PDGF) with the concomitant up-regulation of VEGF. These data suggest that possible involvement of VEGF/Flt-1 system in cytokine-induced mesangial cell proliferations.