Phosphorylation and Function of the Kaposin B Direct Repeats of Kaposi's Sarcoma-Associated Herpesvirus
ABSTRACT
Kaposi's sarcoma-associated herpesvirus encodes a protein, kaposin B, which is composed of multiple copies of 23-amino-acid direct repeats, termed DR2 and DR1. Kaposin B enhances the release of pathogenetically important proinflammatory cytokines by activating the p38 mitogen-activated protein kinase (MAPK)-MK2 kinase pathway and blocking cytokine mRNA decay. Here, we show that this mRNA stabilization function requires both the DR2 and DR1 elements of kaposin B; a monomeric form of the protein consisting of one copy of each repeat retains function. Furthermore, we show that p38 MAPK is capable of directly phosphorylating kaposin B in vitro and map the site of phosphorylation to a specific serine residue in DR1. Mutational ablation of this serine abolishes phosphorylation of the protein by p38 MAPK but does not affect kaposin B's ability to extend mRNA half-life.
FOOTNOTES
- Received 5 November 2005.
- Accepted 28 March 2006.
- ↵*Corresponding author. Mailing address: G.W. Hooper Foundation, University of California—San Francisco, 513 Parnassus Avenue, HSW 1501, Box 0552, San Francisco, CA 94143-0552. Phone: (415) 502-5669. Fax: (415) 476-0939. E-mail: mmccormick{at}ucsf.edu.
- American Society for Microbiology
