HGF-mediated chemotaxis and tubulogenesis require activation of the phosphatidylinositol 3-kinase.

Am J Physiol

Division of Nephrology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.

Published: June 1995

The association of hepatocyte growth factor (HGF) with its high-affinity receptor, c-met, has been shown to induce mitogenesis, motogenesis, and morphogenesis in renal epithelial cells (L. G. Cantley, E. J. G. Barros, M. Gandhi, M. Rauchman, and S. K. Nigam. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F271-F280, 1994), suggesting that HGF may be critical to the orchestration of both renal development and regeneration following injury. Although signal transduction pathways activated by c-met include the phosphatidylinositol 3-kinase (PI-3-kinase), phospholipase C gamma, ras, and others, the activation of PI-3-kinase has been the most striking in vivo. We therefore investigated whether the pathways that mediate phenotypic changes in inner medullary collecting duct cells are altered by inhibition of PI-3-kinase with the fungal metabolite, wortmannin. In these cells, the mean inhibitory concentration for in vitro wortmannin inhibition of PI-3-kinase was approximately 0.2 nM. At this low concentration, motogenesis (quantified by chemotaxis) and morphogenesis (by branching-process formation within collagen matrix) were inhibited in a striking and parallel fashion, while mitogenesis was inhibited to a lesser degree. These experiments suggest that activation of PI-3-kinase is critical for c-met-mediated chemotaxis and tubulogenesis.

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.1995.268.6.F1211DOI Listing

Publication Analysis

Top Keywords

chemotaxis tubulogenesis
8
phosphatidylinositol 3-kinase
8
activation pi-3-kinase
8
inhibition pi-3-kinase
8
pi-3-kinase
5
hgf-mediated chemotaxis
4
tubulogenesis require
4
require activation
4
activation phosphatidylinositol
4
3-kinase association
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!