RELATION OF PROTEIN-KINASE-A AND PROTEIN-KINASE-C TO SIGNALING PATHWAYS OF HEMATOPOIETIC FACTORS IN LEUKEMIA-CELL LINES

In terms of growth, differentiation, and signaling pathways of hematop oietic factors, the effects of protein kinase C (PKC) activator, 12-O- tetradecanoyl-phorbol-13-acetate (TPA) and protein kinase A(PKA) activ ator, dibutyryl cyclic adenosine monophosphate (dbcAMP) were examined in vitro using three factor-responsive myeloid leukemia cell lines. TP A suppressed the growth of OCI/AML-1 and OCI/AML-5 cells but stimulate d the proliferation of OCI/AML-4 cells. TPA differentiated OCI/AML-4 a nd OCI/AML-5 cells to macrophage-like cells. dbcAMP suppressed the gro wth of the three without differentiation. The stimulation of TPA induc ed tyrosine phosphorylation of some proteins in OCI/AML-4 and OCI/AML- 5 cells. Their molecular weights were the same as those phosphorylated by hematopoietic factors. The patterns of phosphorylated proteins wer e different between the two. TPA induced the phosphorylation of MAP ki nase, but not that of JAK2 protein in three cell lines. The stimulatio n of dbcAMP did not induce tyrosine phosphorylation in three cell line s. Overnight exposure of TPA inhibited the tyrosine phosphorylation in duced by hematopoietic factors, although that of dbcAMP did not. We su ggest a close relation of PKC to signaling pathways of hematopoietic f actors, however, the ways of relation were diverse among the cell line s and the clear mechanism explaining its effects on growth and differe ntiation was not elucidated.