The heterodimer of alpha4 and PP2Ac is associated with S6 kinase1 in B cells.
Alpha4 is a signal transduction molecule that is required for B cell activation. Alpha4 associates with the catalytic subunit of protein phosphatase 2A (PP2Ac) and regulates its enzymatic activity. We examined the interaction of alpha4/PP2Ac with S6 kinase1 (S6K1) as a potential downstream signal transduction molecule because both alpha4/PP2Ac association and S6K1 activity were rapamycin-sensitive. Stimulation of spleen B cells with lipopolysaccharide induced the interaction of alpha4/PP2Ac and S6K1. Pull-down assay demonstrated that alpha4 interacts with S6K1 through PP2Ac. S6K1 and alpha4 bind to the different regions of PP2Ac as S6K1 to the region from amino acid 88th to 309th of PP2Ac and alpha4 to the two separated regions of the amino-terminal (from amino acid 19th to 22nd) and the middle (from 150th to 164th) portions of PP2Ac. These results suggest that alpha4 regulates S6K1 activity through PP2Ac in B cell activation.
Yamashita
Takeshi
T
Department of Immunology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
Inui
Seiji
S
Maeda
Kazuhiko
K
Hua
Ding Rong
DR
Takagi
Katsumasa
K
Sakaguchi
Nobuo
N
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D001483:Base Sequence; D017931:DNA Primers; D019281:Dimerization; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D054648:Protein Phosphatase 2; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C092377:Igbp1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D010750:Phosphoproteins; D019893:Ribosomal Protein S6 Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2