Inhibition of Src by direct interaction with protein phosphatase 2A.
In this study, we report that Src kinase is inhibited by protein phosphatase 2A (PP2A), a serine/threonine phosphatase. We carried out experiments in vitro using purified PP2A (AC dimer) and full-length v-Src or truncated forms of v-Src. The inhibition of v-Src by PP2A is concentration- and time-dependent. Addition of okadaic acid, a PP2A phosphatase inhibitor, abolished the PP2A-dependent inhibition of v-Src. When experiments were carried out at 4 degrees C under conditions where PP2A activity is inhibited, Src activity was unaffected by the presence of PP2A, suggesting that PP2A binding alone is insufficient to block Src activity. These results imply that PP2A activity is essential for inhibition of v-Src. We also demonstrate that PP2A binds to the catalytic and the regulatory domains of v-Src.
Yokoyama
N
N
Department of Physiology and Biophysics, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-8661, USA.
Miller
W T
WT
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D005982:Glutathione Transferase / Q000378:metabolism; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D019061:src-Family Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2