Protein kinase C and mitogen‐activated protein kinase signalling in oligodendrocytes

Abstract

Oligodendrocytes (OL) play a significant physiological role in the central nervous system by creating the myelin sheath that allows for the efficient conduction of nerve impulses. Therefore, it is important to understand which signalling cascades define the proliferation, differentiation, survival, and myelin formation potential of these cells. Currently, much of the knowledge in this field has focused on two sets of protein kinase signalling molecules: Protein kinase C (PKC) and the mitogen-activated protein kinases (MAPKs). The roles of these kinases in OL are complex, and appear to be highly dependent on the developmental stage of the OL. Even so, some broad conclusions can be drawn from the multitude of experiments conducted on the roles of PKC and MAPKs in OL. For instance, PKC appears to have a proliferative effect on immature OL, while at the same time having an inhibitory effect on OL differentiation. In mature OL, the effects of PKC include increased process extension and myelin formation. The extracellular signal-regulated (ERK) members of the MAPK family also appear to increase process extensions in mature OL. On the other hand, the c-Jun N-terminal kinase (JNK) and p38 kinase members of the MAPK family appear to regulate apoptotic events in OL.

Membrane-anchoring and Charge Effects in the Interaction of Myelin Basic Protein with Lipid Bilayers Studied by Site-directed Spin Labeling

“…The sequence of PRTP represents a PXXP motif that can bind to an SH3 domain (Src homology 3) containing protein such as non-receptor tyrosine kinases (44). Moreover, the threonyl residue within this motif is a mitogen-activated protein kinase target (45). Our results suggest that this segment of MBP is naturally exposed and available for modification and recognition.…”

Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C

“…This correlates well with our data showing that MASS1 regulates MAG protein stability. PKC signaling has a proliferative effect on immature OLs and increases process extension and myelin formation in mature OLs (26). PKC activation also results in increased phosphorylation of CNPase and MBP.…”

Signaling Cascades Activated upon Antibody Cross-linking of Myelin Oligodendrocyte Glycoprotein

“…Response of OLs to Anti-MOG Alone Compared with MOG Cross-linking-Extracellular signal-regulated kinase members of the MAPK kinase family, in close association with phosphatidylinositol 3-kinase and its downstream effector Akt (24), promote OL survival (25,26). Further investigation showed that in contrast to the other phosphoproteins that required MOG cross-linking, e.g.…”

“…These signaling modifications appear to be lipid raftindependent, since neither MOG, MAPK, or Akt are found in these microdomains under these conditions. Further, since the Akt, and probably MAPK, pathways promote survival of OLs (25,26), these changes may have implications in the normal physiology of the cell, in which stimulation of MOG with a hypothetical ligand may support survival of OLs. Upon further cross-linking the MOG⅐anti-MOG complexes by anti-IgG antibodies, MOG becomes repartitioned into detergent-insoluble complexes, at least half of which exhibit characteristics of lipid rafts.…”