Antigen receptors on B and T lymphocytes transduce signals by activati
ng nonreceptor protein tyrosine kinases (PTKs). A family of receptor P
TKs contains kinase insert regions with the sequence tyrosine-X-X-meth
ionine (where X is any amino acid) that when phosphorylated mediate th
e binding and activation of phosphatidylinositol 3-kinase (PI 3-kinase
). The CD19 membrane protein of B cells enhances activation through me
mbrane immunoglobulin M (mIgM) and was found to contain a functional a
nalog of the kinase insert region. Ligation of mIgM induced phosphoryl
ation of CD19 and association with PI 3-kinase. Thus, CD19 serves as a
surrogate kinase insert region for mIgM by providing the means for PI
3-kinase activation by nonreceptor PTKs.