Phosphorylation
of tyrosine residues within the accessory chains ITAMS represents the first BCR/TCR-mediated
intracellular event following
antigen receptor stimulation.
This initial
phosphorylation is carried out by Src-family kinases: Fyn, Blk and Lyn in B-cells and Lck and Fyn in T-cells.
In B cells, these
kinases associate with the ITAMs
of the Igα and Igβ chains through (1) low affinity interactions with their amino-terminal domains or (2) single pTyr ITAMs via SH2 domains (shown here).
Clustering of
BCRs brings many of these associated
Src kinases together where they can
phosphorylate each other and also the ITAMs of Igα and Igβ.
Phosphorylation
of a single tyrosine in these
ITAMs allows tighter binding of Src kinases
through their SH2 domains. These bound
kinases act to phosphorylate more neighboring
ITAMs and provide substrates for
Syk