Urea and nacl differentially regulate focal adhesion kinase (fak) and raftk/pyk2 in mimcd3 renal medullary cells. Avraham, Zheng Zhang Hava, and David M. Cohen. 1Division of Nephrology, Oregon Health Sciences University and the Portland V.A. Medical Center, Portland, OR 97207, and 2Division of Experimental Medicine and Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215
APStracts 5:0109F, 1998.
Two cytosolic tyrosine kinases, focal adhesion kinase (FAK) and the newly described FAK homologue, related adhesion focal tyrosine kinase (RAFTK, also called PYK2 and CAKb), have been implicated in signaling to multiple mitogen-activated protein kinase (MAPK) pathways. Therefore, the ability of NaCl and urea to activate these kinases was investigated by in vitro kinase assay and antiphosphotyrosine immunoblotting. RAFTK was promptly but only transiently activated by urea (within 1 minute; 45%), whereas NaCl activated this kinase at 1, 5, 15, and 30 minutes of treatment by (35-60%). In contrast, FAK exhibited only subtle regulation by the two solutes, however the time course of induction was distinct for each solute. NaCl activated FAK at 1, 5, and 15 minutes (25-40%), whereas urea-inducible FAK activation (30%) was not evident until fully 15 minutes of treatment. At 5 minutes of treatment with increasing concentrations of solute, both urea and NaCl activated RAFTK in a dose-dependent and comparable fashion, culminating in an approximately two-fold activation at 800 mosm solute. Consistent with these data, solute treatment also enhanced tyrosine phosphorylation of RAFTK.

Received 23 May 1997; accepted in final form 11 June 1998.
APS Manuscript Number F174-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 30 July 1998