Protein kinase C and c-myc gene activation pathways in thrombopoietin signal transduction.
Thrombopoietin (TPO) is the major regulator of the proliferation and differentiation of megakaryocyte precursors through interaction with its receptor encoded by the c-mpl protooncogene. We established the human TPO-dependent leukemia cell line, UT-7/TPO (Blood 87, 4552, 1996). In these cells, TPO activated protein kinase C (PKC) in a time dependent manner. Subsequently, the c-myc gene was transiently induced to a maximal level 60-90 minutes after TPO exposure. In addition, we found that stimulating UT-7/TPO cells with TPO rapidly induces the significant accumulation of inositol 1, 4, 5-trisphosphate (Ins-P3), leading to the mobilization of calcium from intracellular stores. Taken together, the activation of PKC and subsequent c-myc gene induction are involved in the TPO-induced cellular response(s), presumably through the activation of PLC.
Kunitama
M
M
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Shimizu
R
R
Yamada
M
M
Kato
T
T
Miyazaki
H
H
Okada
K
K
Miura
Y
Y
Komatsu
N
N
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013926:Thrombopoietin / Q000378:metabolism*; D015533:Transcriptional Activation; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007527:Isoenzymes; D011994:Recombinant Proteins; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D013926:Thrombopoietin; D011493:Protein Kinase C; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium