Unique features of HIV-1 Rev protein phosphorylation by protein kinase CK2 ('casein kinase-2') |
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Authors: | Marin O Sarno S Boschetti M Pagano M A Meggio F Ciminale V D'Agostino D M Pinna L A |
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Affiliation: | Dipartmento di Chimica Biologica and Centro del CNR per lo Studio delle Biomembrane, Università delgi Studi di Padova, Padua, Italy. |
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Abstract: | The HIV-1 Rev transactivator is phosphorylated in vitro by protein kinase CK2 at two residues, Ser-5 and Ser-8; these sites are also phosphorylated in vivo. Here we show that the mechanism by which CK2 phosphorylates Rev is unique in several respects, notably: (i) it is fully dependent on the regulatory, beta-subunit of CK2; (ii) it relies on the integrity of an acidic stretch of CK2 beta which down-regulates the phosphorylation of other substrates; (iii) it is inhibited in a dose-dependent manner by polyamines and other polycationic effectors that normally stimulate CK2 activity. In contrast, a peptide corresponding to the amino-terminal 26 amino acids of Rev, including the phosphoacceptor site, is readily phosphorylated by the catalytic subunit of CK2 even in the absence of the beta-subunit. These data, in conjunction with the observation that two functionally inactive derivatives of Rev with mutations in its helix-loop-helix motif are refractory to phosphorylation, indicate the phosphorylation of Rev by CK2 relies on conformational features of distinct regions that are also required for the transactivator's biological activity. |
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