Abstract:
:We investigated the possible relationship between the susceptibility of cells to differentiation induced by phorbol 12-myristate 13-acetate (PMA) and the subcellular translocation of calcium- and phospholipid-dependent protein kinase (protein kinase C) activity from the cytosol to the membrane. These two events were analyzed in a number of human leukemia cell lines, including four cell variants of the promyelocytic cell line HL-60 that exhibit different degrees of susceptibility to PMA-induced differentiation. The phenotype of the differentiated cells was characterized by increased reactivity with monoclonal antibodies against maturation-specific cell surface antigens, increased nonspecific esterase activity, and acquisition of morphological cell maturation. Analysis of the subcellular distribution of protein kinase C activity in each of these cell types revealed that 90% of the kinase activity was present in the cytosolic fraction, with the remaining activity in the membrane fraction. Treatment of the differentiation-susceptible cells with 160 nM PMA resulted, within 5 min after treatment, in a greater than 60% decrease in protein kinase C activity in the cytosolic fraction and a greater than 1500% increase in the activity in the membrane fraction. No such subcellular redistribution of protein kinase C activity was found after treatment of the differentiation-resistant cells. On the basis of these findings, we suggest that the process of subcellular translocation of protein kinase C activity, initiated after the binding of PMA to this kinase, is required for the induction of cell differentiation by this phorbol diester.
journal_name
Proc Natl Acad Sci U S Aauthors
Homma Y,Henning-Chubb CB,Huberman Edoi
10.1073/pnas.83.19.7316subject
Has Abstractpub_date
1986-10-01 00:00:00pages
7316-9issue
19eissn
0027-8424issn
1091-6490journal_volume
83pub_type
杂志文章abstract::Network theory provides a powerful tool for the representation and analysis of complex systems of interacting agents. Here, we investigate the U.S. House of Representatives network of committees and subcommittees, with committees connected according to "interlocks," or common membership. Analysis of this network revea...
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