Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus-associated ERK-2 kinase.
L-domain-containing proteins from animal retroviruses play a critical role in the recruitment of the host cell endocytic machinery that is required for retroviruses budding. We recently demonstrated that phosphorylation of the p6(gag) protein containing the L-domain of the human immunodeficiency virus type 1 regulates viral assembly and budding. Here, we investigated whether or not the L-domain-containing protein from another human retrovirus, namely the matrix protein of the human T-cell leukemia virus type 1, that contains the canonical PTAP and PPPY L-domain motifs, shares similar functional properties. We found that MA is phosphorylated at several sites. We identified one phosphorylated amino acid in the HTLV-1 MA protein as being S105, located in the close vicinity to the L-domain sequence. S105 phosphorylation was found to be mediated by the cellular kinase ERK-2 that is incorporated within HTLV-1 virus particles in an active form. Mutation of the ERK-2 target S105 residue into an alanine was found to decrease viral release and budding efficiency of the HTLV-1(ACH) molecular clone from transfected cells. Our data thus support the postulate that phosphorylation of retroviral L-domain proteins is a common feature to retroviruses that participates in the regulation of viral budding.
Hémonnot
Bénédicte
B
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, Centre National pour la Recherche Scientifique UMR5121-Université Montpellier 1, Institut de Biologie, 4 Boulevard Henri IV, CS89508, 34960 Montpellier cedex 2, France.
Molle
Dorothée
D
Bardy
Martine
M
Gay
Bernard
B
Laune
Daniel
D
Devaux
Christian
C
Briant
Laurence
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development* / Q000378:metabolism*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012694:Serine / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly
D014763:Viral Matrix Proteins; D012694:Serine; D019950:Mitogen-Activated Protein Kinase 1