The regulation of antigen-receptor signaling by protein tyrosine phosphatases: a hole in the story

Antigen-receptor signaling requires Src-family kinases to initiate tyrosine phosphorylation. CD45 dephosphorylates the inhibitory site in Src-family kinases before antigen-receptor engagement and thus serves to ‘prime’ the kinases. It has been unclear why CD45 does not also dephosphorylate ‘activated’ kinases or motifs within the cytoplasmic domains of antigenreceptors and thus prevent signal transduction. Recent reports raise the possibility that CD45 is excluded from engaged antigen-receptors by mechanisms that may include the formation of lipid microdomains.