J Korean Med Sci.  1993 Dec;8(6):413-419. 10.3346/jkms.1993.8.6.413.

Phosphorylation of ribosomal protein S6 and its regulation during differentiation of human leukemic cells

Affiliations
  • 1Department of Pharmacology, Catholic University Medical College, Seoul, Korea.

Abstract

We attempted to study the role of protein tyrosine kinase (PTK) and protein kinase C (PKC) in the cascade of phosphorylation of ribosomal protein S6 during differentiation of leukemic cells (HL-60, THP-1, and RWLeu-4). Neither activation nor inhibition of colony stimulating factor-1 (CSF-1) receptor's PTK activity with CSF-1 or genistein respectively affected the phosphorylation of S6. However, vanadate which is a protein tyrosine phosphatase (PTP) inhibitor showed enhancement of S6 phosphorylation. Dimethylsulfoxide which does not affect either PTK or PKC demonstrated no change in S6 phosphorylation. PKC activation by acute 12-0-tetradecanoyl phorbol-13-acetate (TPA) treatment induced monocytic differentiation and S6 phosphorylation. Surprisingly, the more prominent phosphorylation of S6 protein was observed in PKC-depleted cells by prolonged TPA treatment. Our results suggest that PTK/PTP play a lesser role in S6 phosphorylation of HL-60 cells than PKC does. In addition, two different mechanisms seem to be involved in TPA-induced S6 phosphorylation during HL-60 differentiation: PKC activation by acute TPA treatment and PKC depletion which may lead to the synthesis of some endogenous protein responsible for the differentiation by chronic TPA treatment.

Keyword

Differentiation; S6; TPA; Protein kinase C; Protein tyrosine kinase

MeSH Terms

Cell Differentiation
Humans
Leukemia/*metabolism/pathology
Macrophage Colony-Stimulating Factor/pharmacology
Phosphorylation
Protein Kinase C/physiology
Protein-Tyrosine Kinases/physiology
Ribosomal Protein S6
Ribosomal Proteins/*metabolism
Tetradecanoylphorbol Acetate/pharmacology
Tumor Cells, Cultured
Ribosomal Protein S6
Ribosomal Proteins
Tetradecanoylphorbol Acetate
Macrophage Colony-Stimulating Factor
Protein-Tyrosine Kinases
Protein Kinase C
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