Effects of tyrosine kinase inhibitors on protein kinase-independent systems.
Tyrosine kinase inhibitors have been widely used to probe the role of tyrosine phosphorylation in cellular signalling. These inhibitors exhibit an apparent specificity for tyrosine kinases over the serine/threonine kinases but little is known about their effects on other enzymes or biological systems. We demonstrate that genistein, erbstatin and alpha-cyanocinnamamides (tyrphostins) have inhibitory effects on fatty acid synthesis, lactate transport, mitochondrial oxidative phosphorylation and aldehyde dehydrogenase. We propose, therefore, that results obtained using tyrosine kinase inhibitors should be interpreted with caution, particularly if used at concentrations sufficient to inhibit these non-protein kinase-dependent events.
Young
S W
SW
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Poole
R C
RC
Hudson
A T
AT
Halestrap
A P
AP
Denton
R M
RM
Tavaré
J M
JM
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002396:Catechols / Q000494:pharmacology; D005227:Fatty Acids / Q000096:biosynthesis; D019833:Genistein; D006873:Hydroquinones / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020032:Tyrphostins; D014475:Uncoupling Agents / Q000494:pharmacology
D002396:Catechols; D005227:Fatty Acids; D006873:Hydroquinones; D007529:Isoflavones; D007773:Lactates; D009570:Nitriles; D011773:Pyruvates; D020032:Tyrphostins; D014475:Uncoupling Agents; C060152:tyrphostin 47; D019833:Genistein; D000444:Aldehyde Dehydrogenase; D011505:Protein-Tyrosine Kinases; C048212:erbstatin