Dephosphorylation of specific proteins in HL-60 cells by 1 alpha, 25-dihydroxyvitamin D3: possible involvement of cAMP-dependent protein kinase.
Changes of phosphoprotein patterns in HL-60 cells were studied during short exposures to 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. One hundred nanometers 1,25(OH)2D3 dephosphorylated at least three proteins in 6 h: phosphoproteins with molecular weights of 82 kD (pp82), 33 kD (pp33), and 31 kD (pp31). Phosphorylation of pp33 and pp31 was also suppressed by 1 mM dbcAMP, and dephosphorylation of the two protein by 1,25(OH)2D3 was inhibited by 8 microM H-8, an inhibitor of cAMP-dependent protein kinase (PKA). Furthermore, 8 microM H-8 inhibited dephosphorylation of the two proteins when it was added with 1,25(OH)2D3. On the other hand, 10 nM TPA gave no significant change to these two phosphoproteins. These results suggest the possibility that PKA is involved in the early stages of 1,25(OH)2D3-induced HL-60 cell differentiation through specific protein dephosphorylation.
Ueda
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Sawada
H
H
Okuda
T
T
Yumoto
Y
Y
Kato
Y
Y
Ogawa
K
K
Tashima
M
M
Yoshida
Y
Y
Okuma
M
M
D003994:Bucladesine / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology*
D009363:Neoplasm Proteins; D010750:Phosphoproteins; D003994:Bucladesine; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D002117:Calcitriol