The tyrosine activation motif as a target of protein tyrosine kinases and SH2 domains.

The signaling subunits of antigen receptor and Fc receptor complexes carry a tyrosin-based activation motif (ITAM). Work of the recent years showed that this motif is required for the activation of protein tyrosine kinases (PTK) via these receptors. We discuss here two models of how ITAM either in its phosphorylated or unphosphorylated state may interact with PTKs. After receptor cross-linking the activated PTKs will also phosphorylate the tyrosines of ITAM. We have found that different members of the src-family of kinases can phosphorylate either both tyrosines or only the first tyrosine of ITAM. We further discuss how this alternative phosphorylation of ITAM can result in the interaction of the BCR with different SH2-containing proteins and thus influence the signal transduction from the receptor.