Myelin basic protein (MBP) is a key component of myelin, the specialized lipid membrane that encases the axons of all neurons. Both plasminogen (Pg) and tissue-type plasminogen activator (t-PA) bind to MBP with high affinity. We investigated the kinetics and mechanisms involved in this process using immobilized MBP and found that Pg activation by t-PA is significantly stimulated by MBP. This mechanism involves the binding of t-PA via a lysine-dependent mechanism to the Lys(91) residue of the MBP NH2-terminal region Asp(82) -Pro(99), and the binding of Pg via a lysine-dependent mechanism to the Lys(122) residue of the MBP COOH-terminal region Leu(109) -Gly(126). In this context, MBP mimics fibrin and because MBP is a plasmin substrate, our results suggest direct participation of the Pg activation system on MBP physiology. (C) 2017 Elsevier Inc. All rights reserved.