Myosin is an in vivo substrate of the protein tyrosine phosphatase (SHP-1) after mIgM cross-linking.
SHP-1 plays an important role in negative signaling in many cell types. For example, after BCR stimulation in apoptotic B cells, SHP-1 has been shown to be recruited to phosphorylated ITIMs present in receptors such as CD72. However, the SHP-1 substrates in the chicken B cell line, DT40, have been poorly undefined. To identify SHP-1 substrates in DT40, we used a trapping mutant SHP-1 C/S (a catalytically inactive form). BCR stimulation induced hyper-phosphorylation of 230 kDa protein in C/S transfectants. MALDI-TOF/MS analysis revealed that this was myosin carrying ITIM. SHP-1 was shown to bind to this ITIM in synthetic peptide binding experiment. Thus, myosin is a direct SHP-1 substrate in B cells. The results suggest that SHP-1 plays a critical role in the reorganization of cytoskeletal architecture mediated via BCR stimulation.
Baba
Takeshi
T
Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, 278-0022, Chiba, Japan.
Fusaki
Noemi
N
Shinya
Nobuko
N
Iwamatsu
Akihiro
A
Hozumi
Nobumichi
N
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D001665:Binding Sites; D002645:Chickens; D007075:Immunoglobulin M / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D014407:Tumor Cells, Cultured
D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D009218:Myosins