The lipophilic muramyltripeptide MTP-PE, a biological response modifier, is an activator of protein kinase C.
The lipophilic immunomodulator MTP-PE is able to activate purified protein kinase C (PKC) by substituting phosphatidyl-serine (PS) or the synthetic diacylglycerol, DiC8, in the assay system. In addition, MTP-PE inhibited [3H]-phorbol-12, 13-dibutyrate ([3H]-PDBu) binding to PKC in a reconstituted receptor system as well as on intact cells (MCF-7). Furthermore, MTP-PE was also able to reduced the epidermal growth factor binding of MCF-7 cells to an extent similar to that found with DiC8 or PDBu. These data indicate that MTP-PE is able to compete for the phorbol ester binding site on PKC both in vivo and in vitro. The components of the MTP-PE molecule, MTP (muramyl-tripeptide) and PE (phosphatidylethanolamine) exerted only marginal effects on PKC activity, did not affect the phorbol ester binding of PKC and the EGF binding of intact MCF-7 cells. Our results suggest that only the complete molecule of the immunomodulator MTP-PE is able to interact with PKC.
Meyer
T
T
Fabbro
D
D
Eppenberger
U
U
Matter
A
A
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011955:Receptors, Drug; D011971:Receptors, Immunologic / Q000187:drug effects
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010703:Phorbol Esters; D010714:Phosphatidylethanolamines; D011955:Receptors, Drug; D011971:Receptors, Immunologic; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C037144:mifamurtide; D015240:Phorbol 12,13-Dibutyrate; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035104:muramylNAc-Ala-isoGln-Lys-tripeptide; D066246:ErbB Receptors; D011493:Protein Kinase C