Figure 1.

A tale of three CD4 and CD8-p56^lck complexes and the structure of pp60^src and p56^lck. (A) The model of three CD4 and CD8-p56^lck complexes in T-cells. CD8 is expressed as a CD8α homodimer as well as a CD8α/β heterodimer. p56^lck binds to the α subunit but not the β subunit. CD8α homodimer has two p56^lck bound molecules and the CD8α/β heterodimer has a single p56^lck bound. CD4 binds to p56^lck in a monomeric form. (B) Structure of pp60^src and p56^lck. p56^lck is an immune cell-enriched member of the pp60^src family of protein-tyrosine kinases. p56^lck is myristoylated and palmitoylated at the N-terminus, while Src lacks palmitoylation sites. This region is followed by poorly conserved unique SH4 region which in the case of p56lck binds to the cytoplasmic tails of CD4 and CD8, an SH3 domain that binds to proline-rich residues, an SH2 domain that binds to specific sites that are tyrosine phosphorylated, an SH2-kinase linker region, an SH1 kinase domain followed by a C-terminal negative regulatory region. The C-terminal tail has an inhibitory Y-527 site when phosphorylated, in the case of pp60^src and a Y-505 site in p56^lck. pp60^src and p56^lck also possess an auto-phosphorylation site in the kinase domain of each kinase corresponding to Y-416 in the case of pp60^src and Y-394 in the case of p56^lck.