CD45 Modulates Phosphorylation of Both Autophosphorylation and Negative Regulatory Tyrosines of Lyn in B Cells

• Published in: The Journal of biological chemistry Vol. 271; no. 48; pp. 30487 - 30492
• Main Authors: Yanagi, Shigeru, Sugawara, Hitoshi, Kurosaki, Mari, Sabe, Hisataka, Yamamura, Hirohei, Kurosaki, Tomohiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.11.1996; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; B-Lymphocytes - physiology; Calcium - physiology; Cell Compartmentation; Cells, Cultured; Chickens; Leukocyte Common Antigens - metabolism; Mutagenesis, Insertional; Peptide Mapping; Phosphorylation; Phosphotyrosine - metabolism; Signal Transduction; src-Family Kinases - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.48.30487

CD45 is a tyrosine phosphatase that is required for normal B cell receptor (BCR)-mediated signaling. It has been shown that Src-family tyrosine kinases such as Lyn could be a potential substrate for CD45. In vitro studies indicate that activities of Src family tyrosine kinases are regulated by tyrosine phosphorylation; C-terminal phosphorylation is inhibitory, and autophosphorylation is stimulatory. We report here that both autophosphorylation and C-terminal negative regulatory tyrosines of Lyn were hyperphosphorylated in CD45-deficient DT40 B cells. In this mutant cell, BCR-induced protein-tyrosine phosphorylation and calcium mobilization were severely compromised, as seen in Lyn-deficient cells. Consistent with this observation, Lyn activation upon receptor ligation was profoundly decreased in CD45-deficient cells. Taken together, our results suggest that dephosphorylation of tyrosine residues at both autophosphorylation and negative regulatory sites is mediated by CD45 in vivo, and that dephosphorylation of C-terminal tyrosine is a prerequisite for participation of Lyn in BCR signaling.