TAT-ASSOCIATED KINASE, TAK, ACTIVITY IS REGULATED BY DISTINCT MECHANISMS IN PERIPHERAL-BLOOD LYMPHOCYTES AND PROMONOCYTIC CELL-LINES

TAK, a multisubunit cellular protein kinase that specifically associat es with the human immunodeficiency virus Tat proteins and hyperphospho rylates the carboxyl-terminal domain of RNA polymerase II, is a cofact or for Tat and mediates its transactivation function. The catalytic su bunit of TAK has been identified as cyclin-dependent kinase Cdk9, and its regulatory partner has been identified as cyclin T1; these protein s are also components of positive transcription elongation factor P-TE Fb. TAK activity is up-regulated upon activation of peripheral blood l ymphocytes and following macrophage differentiation of promonocytic ce ll lines. We have found that activation of peripheral blood lymphocyte s results in increased mRNA and protein levels of both Cdk9 and cyclin TI. Cdk9 and cyclin T1 induction occurred in purified CD4(+) primary T cells activated by a variety of stimuli. In contrast, phorbol ester- induced differentiation of promonocytic cell lines into macrophage-lik e cells produced a large induction of cyclin T1 protein expression fro m nearly undetectable levels, while Cdk9 protein levels remained at a constant high level. Measurements of cyclin T1 mRNA levels in a promon ocytic cell line suggested that regulation of cyclin T1 occurs at a po sttranscriptional level. These results suggest that cyclin T1 and TAK function may be required in differentiated monocytes and further show that TAK activity can be regulated by distinct mechanisms in different cell types.