IDENTIFICATION OF A MITOGEN-ACTIVATED PROTEIN-KINASE SITE IN HUMAN MYELIN BASIC-PROTEIN IN-SITU

Ultrastructural localization of a specific phosphorylated isomer of my elin basic protein (MBP) has been achieved with a monoclonal antibody specific for human MBP sequence, 89-105, in which Thr(98) was phosphor ylated. Cryosections of human brain white matter revealed that gold pa rticles were found localized almost exclusively to the major dense lin e demonstrating that threonine 98 in the sequence Thr-Pro-Arg-Thr-Pro- Pro-Pro, a mitogen-activated protein kinase-specific site, was phospho rylated in vivo. In two cases of multiple sclerosis, the density of go ld particles in myelin was reduced by about 30%, in one case by 42%, a nd by 80% in a fourth case. However, gold labelling was seen in areas of demyelination suggesting that the phosphorylated threonyl peptide w as protected from degradation.