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Unique features of HIV‐1 Rev protein phosphorylation by protein kinase CK2 (‘casein kinase‐2’)
Author(s) -
Marin Oriano,
Sarno Stefania,
Boschetti Marco,
Pagano Mario A,
Meggio Flavio,
Ciminale Vincenzo,
D'Agostino Donna M,
Pinna Lorenzo A
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01971-2
Subject(s) - phosphorylation , casein kinase 2 , protein subunit , transactivation , kinase , protein kinase a , biochemistry , phosphorylation cascade , cyclin dependent kinase 2 , protein phosphorylation , biology , chemistry , microbiology and biotechnology , transcription factor , gene
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, β‐subunit of CK2; (ii) it relies on the integrity of an acidic stretch of CK2β 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 β‐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.