Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk

• Published in: Biochemical and biophysical research communications 2007-12, Vol.364 (1), p.111-117
• Main Authors: Adachi, Takahiro, Wienands, Jürgen, Tsubata, Takeshi, Kurosaki, Tomohiro
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; B lymphocyte; BCR; Calcium Signaling - physiology; Cell Line; Chickens; Humans; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Molecular Sequence Data; Protein Structure, Tertiary; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Signal Transduction; Signaling; Swine; Syk; Syk Kinase; Tyrosine kinase; ZAP-70 Protein-Tyrosine Kinase - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.09.100

Non-receptor type protein tyrosine kinase (PTK) Syk is essential for the signaling via the B cell antigen receptor (BCR). Upon BCR crosslinking, Syk is recruited via its tandem SH2 domains to tyrosine-phosphorylated Ig-α/Ig-β constituting components of BCR, and is then activated. The interdomain A lying between the two SH2 domains is highly conserved among different species of Syk and between Syk and ZAP-70. The mutant Syk carrying a deletion in the interdomain A (Δ140–159) became phosphorylated regardless of BCR ligation and did not induce Ca 2+ mobilization upon crosslinking of BCR. Furthermore, in vitro binding assay revealed that deletion of a part of the interdomain A abolished its binding activity to phosphorylated Ig-α/Ig-β. These results indicate that the interdomain A of Syk is required for activation of Syk by binding to the phosphorylated Ig-α/Ig-β upon BCR ligation and inhibition of spontaneous activation at the resting state.