COUNTERREGULATION BY THE CORECEPTORS CD19 AND CD22 OF MAP KINASE ACTIVATION BY MEMBRANE IMMUNOGLOBULIN

The signaling pathways linked to membrane immunoglobulin (mig) that ar e regulated by the coreceptors CD19 and CD22 are not known. The mitoge n-activated protein (MAP) kinases ERK2, JNK, and p38 couple extracellu lar signals to transcriptional responses. The capacity of mig to activ ate these MAP kinases is synergistically amplified by coligating CD19, and this effect requires that CD19 be juxtaposed to mig. CD22 suppres ses MAP kinase activation when cross-linked to mig alone or to the col igated complex of mig and CD19. Separate ligation and sequestration of CD22 from mig enhances MAP kinase activation, probably reflecting rel ease of mig from constitutive down-regulation. Thus, CD19 and CD22 hav e counterregulatory effects on MAP kinase activation by mig, which are dependent on their proximity to the antigen receptor.