Interdomain A is crucial for ITAM-dependent and -independent regulation of Syk.
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-alpha/Ig-beta 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 (Delta140-159) became phosphorylated regardless of BCR ligation and did not induce Ca2+ 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-alpha/Ig-beta. These results indicate that the interdomain A of Syk is required for activation of Syk by binding to the phosphorylated Ig-alpha/Ig-beta upon BCR ligation and inhibition of spontaneous activation at the resting state.
Adachi
Takahiro
T
Laboratory of Immunology, Biomedical Science, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. tadachi.imm@mri.tmd.ac.jp
Wienands
Jürgen
J
Tsubata
Takeshi
T
Kurosaki
Tomohiro
T
D000595:Amino Acid Sequence; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D002645:Chickens; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013552:Swine; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase