CD2 is a surface receptor expressed on the majority of thymocytes, T cells and NK cells. CD2 associates with the Src-family kinases p56;Using mutational analysis, I have demonstrated that the fourth proline-rich domain is critical for Fyn SH3 domain binding. Mutation of the first, second and the fourth domain of CD2 (CD2-m124) was necessary to completely abolish Itk binding, suggesting that multiple proline-rich domains are involved in binding to the SH3 domain of Itk. While mutation of a single proline-rich region was insufficient to inhibit CD2-mediated NFAT activation, mutation of domain 1, 2 and 4 markedly blocked the activation of NFAT by CD2, further suggesting that multiple proline-rich domains of CD2 are involved CD2 signaling. |