12-O-Tetradecanoylphorbol-13-acetate-induced dephosphorylation of protein kinase Calpha correlates with the presence of a membrane-associated protein phosphatase 2A heterotrimer.
Protein kinase C signaling is desensitized through a combination of dephosphorylation and proteolysis in intact cells. The process of dephosphorylation is analyzed here, as well as its relationship to degradation. It is established for protein kinase Calpha that dephosphorylation occurs in a membrane compartment following activation and temporally preceding significant degradation. The phosphatase responsible for the dephosphorylation appears to be a heterotrimeric type 2A phosphatase, which is shown to be in part constitutively membrane associated. Consistent with a role for this activity, okadaic acid is shown to inhibit the phorbol ester-induced dephosphorylation of protein kinase C that occurs in intact cells. Furthermore, phorbol ester-induced down-regulation of protein kinase Calpha is shown not to be dependent on the rate of dephosphorylation, indicating that these desensitizing pathways may operate in parallel.
Hansra
G
G
Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Bornancin
F
F
Whelan
R
R
Hemmings
B A
BA
Parker
P J
PJ
D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000201:enzymology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D054648:Protein Phosphatase 2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007527:Isoenzymes; D019319:Okadaic Acid; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D013755:Tetradecanoylphorbol Acetate