Myelin basic protein and myelin basic protein peptides induce the proliferation of Schwann cells via ganglioside GM1 and the FGF receptor

Myelin basic protein (MBP) and two peptides derived from MBP (MBP1-44 and M BP152-167) stimulated Schwann cell (SC) proliferation in a cAMP-mediated pr ocess. The two mitogenic regions of MBP did not compete with one another fo r binding to SC suggesting a distinctive SC receptor for each mitogenic pep tide. Neutralizing antibodies to the fibroblast growth factor receptor bloc ked the mitogenic effect of the myelin-related SC mitogen found in the supe rnatant of myelin-fed macrophages. The binding of I-125-MBP to Schwann cell s was specifically inhibited by basic fibroblast growth factor (bFGF) and c onversely the binding of I-125-bFGF was competitively inhibited by MBP. The se data suggested that the mitogenic effect of one MBP peptide was mediated by a bFGF receptor. The binding of MBP to ganglioside GM1 and the ability of MBP peptides containing homology to the B subunit of cholera toxin (whic h binds ganglioside GM1 ) to compete for the binding of a mitogenic peptide (MBP1-44) to SC, identified ganglioside GM1 as a second SC receptor. Based on these results, we conclude that MBP1-44 and MBP152-167 associate with g anglioside GM1 and the bFGF receptor respectively to stimulate SC mitosis.