Phosphorylation and function of the kaposin B direct repeats of Kaposi's sarcoma-associated herpesvirus.
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.
McCormick
Craig
C
Howard Hughes Medical Institute, University of California-San Francisco, CA 94143-0552, USA. mmccormick@ucsf.edu
Ganem
Don
D
D001665:Binding Sites; D016207:Cytokines / Q000235:genetics; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D020871:RNA Stability; D012694:Serine; D014764:Viral Proteins / Q000378:metabolism* / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D016207:Cytokines; D014764:Viral Proteins; C120136:kaposin B protein, Human herpesvirus 8; D012694:Serine; D048051:p38 Mitogen-Activated Protein Kinases