Regulation of biosynthesis and phosphorylation of P210bcr/abl protein during differentiation induction of K 562 cells.
The changes of P210bcr/abl and other tyrosine phosphorylated proteins in K562 cells during growth and differentiation were studied by metabolic labeling with 32PO4 and immunoprecipitation with anti-phosphotyrosine sera. The anti-phosphotyrosine sera recognized P210bcr/abl and other phosphoproteins with mol wt of 150, 115, 100, 70 and 64 kD. The 2-day incubation of K562 cells with inducers for differentiation, hemin, sodium butyrate and TPA, decreased the level of P210bcr/abl protein and other phosphoproteins. Inhibitors of tyrosine protein kinase, amiloride and genistein, also reduced the phosphorylation of P210bcr/abl protein and other substrates, but did not induce differentiation of the cells. Although most of these additives inhibited the cell growth, cytotoxic agents such as adriamycin, vincristine and Ara-C did not affect the level of P210bcr/abl protein. The experiments using 35S-methionine labeled cells and the immunoprecipitation with anti-abl sera suggested that reduced biosynthesis but not dephosphorylation of P210bcr/abl protein mainly accounted for the reduction of P210bcr/abl protein reacting to anti-phosphotyrosine sera in differentiation-induced cells. These results indicate that the reduction of P210bcr/abl protein synthesis plays some roles in cellular differentiation of K562 cells.
Nishimura
J
J
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Takahira
H
H
Shibata
K
K
Muta
K
K
Yamamoto
M
M
Ideguchi
H
H
Umemura
T
T
Nawata
H
H
D002454:Cell Differentiation / Q000187:drug effects; D002458:Cell Fractionation; D002460:Cell Line; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011233:Precipitin Tests; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr; D014443:Tyrosine / Q000031:analogs & derivatives / Q000276:immunology
D006133:Growth Substances; D007106:Immune Sera; D010750:Phosphoproteins; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr