TY - JOUR
T1 - Multivalent ganglioside and sphingosine conjugates modulate myelin protein kinases
AU - Mahoney, James A.
AU - Schnaar, Ronald L.
N1 - Funding Information:
We thank S. Plafker and Dr W. Gibson for assistance with phosphoamino acid analysis, Drs K. Walker and R. Cotter of the Middle Atlantic Mass Spectrometry Facility for mass spectrometric analysis of sphingolipid-BSA conjugates, and Dr Y. Yasuda for the disuccinimidyl adipate synthesis of sphingosine-BSA. This work was supported by grants HD14010 and GM07626 from the National Institutes of Health.
PY - 1997/8/14
Y1 - 1997/8/14
N2 - Gangliosides, added exogenously at concentrations of 10-100 μM, inhibit intrinsic protein kinase activities in purified rat brain myelin. Multivalent neoganglioproteins - gangliosides covalently attached, via their lipid moieties, to bovine serum albumin - were much more potent, inhibiting myelin protein phosphorylation half-maximally at a concentration of 100 nM, Different ganglioside conjugates varied 10-fold in inhibitory potency; GT1b-conjugates being the most potent and GM3-conjugates being the least. Conjugates of ganglioside oligosaccharides, lacking the lipid moiety, did not inhibit myelin protein phosphorylation, whereas conjugates of sphingosine inhibited nearly as potently as GT1b conjugates. Conjugate-mediated inhibition of myelin protein phosphorylation was due to inhibition of a protein serine kinase activity rather than activation of a phosphatase activity. We conclude that (i) clustered gangliosides or sphingosine are potent myelin protein kinase inhibitors, and (ii) sphingolipid metabolism is not required for myelin protein kinase inhibition. In contrast to their effects on myelin protein phosphorylation, ganglioside conjugates stimulated phosphorylation of a presumptive axon membrane protein. The data support the conclusion that gangliosides and other sphingolipids, when appropriately clustered, are potent modulators of central nervous system protein phosphorylation.
AB - Gangliosides, added exogenously at concentrations of 10-100 μM, inhibit intrinsic protein kinase activities in purified rat brain myelin. Multivalent neoganglioproteins - gangliosides covalently attached, via their lipid moieties, to bovine serum albumin - were much more potent, inhibiting myelin protein phosphorylation half-maximally at a concentration of 100 nM, Different ganglioside conjugates varied 10-fold in inhibitory potency; GT1b-conjugates being the most potent and GM3-conjugates being the least. Conjugates of ganglioside oligosaccharides, lacking the lipid moiety, did not inhibit myelin protein phosphorylation, whereas conjugates of sphingosine inhibited nearly as potently as GT1b conjugates. Conjugate-mediated inhibition of myelin protein phosphorylation was due to inhibition of a protein serine kinase activity rather than activation of a phosphatase activity. We conclude that (i) clustered gangliosides or sphingosine are potent myelin protein kinase inhibitors, and (ii) sphingolipid metabolism is not required for myelin protein kinase inhibition. In contrast to their effects on myelin protein phosphorylation, ganglioside conjugates stimulated phosphorylation of a presumptive axon membrane protein. The data support the conclusion that gangliosides and other sphingolipids, when appropriately clustered, are potent modulators of central nervous system protein phosphorylation.
KW - GT1b
KW - Glycosphingolipid
KW - Neoglycoprotein
KW - Protein serine kinase
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U2 - 10.1016/S0005-2736(97)00070-9
DO - 10.1016/S0005-2736(97)00070-9
M3 - Article
C2 - 9298942
AN - SCOPUS:0030839410
SN - 0005-2736
VL - 1328
SP - 30
EP - 40
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
IS - 1
ER -