The PI 3-kinase isoforms p110(alpha) and p110(beta) have differential roles in PDGF- and insulin-mediated signaling.
Phosphoinositide 3'-kinases constitute a family of lipid kinases implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Phosphoinositide 3'-kinases that bind to the platelet-derived growth factor receptor are composed of two subunits: the p85 subunit acts as an adapter and couples the catalytic p110 subunit to the activated receptor. There are different isoforms of p85 as well as of p110, the individual roles of which have been elusive. Using microinjection of inhibitory antibodies specific for either p110(alpha) or p110(beta) we have investigated the involvement of the two p110 isoforms in platelet-derived growth factor- and insulin-induced actin reorganization in porcine aortic endothelial cells. We have found that antibodies against p110(alpha), but not antibodies against p110(beta), inhibit platelet-derived growth factor-stimulated actin reorganization, whereas the reverse is true for inhibition of insulin-induced actin reorganization. These data indicate that the two phosphoinositide 3'-kinase isoforms have distinct roles in signal transduction pathways induced by platelet-derived growth factor and insulin.
Hooshmand-Rad
R
R
Ludwig Institute for Cancer Research, BMC, Box 595, S-751 24 Uppsala, Sweden.
Hájková
L
L
Klint
P
P
Karlsson
R
R
Vanhaesebroeck
B
B
Claesson-Welsh
L
L
Heldin
C H
CH
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D015398:Signal Transduction; D013552:Swine
D000199:Actins; D007328:Insulin; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor