Offermanns, S. and Seifert, Roland and Metzger, J. W. and Jung, G. and Lieberknecht, A. and Schmidt, U. and Schultz, Günter
Lipopeptides are effective stimulators of tyrosine phosphorylation in human myeloid cells.
Biochemical Journal 282 ( Pt 2, pp. 551-7.
Synthetic lipopeptide analogues of the N-terminus of bacterial lipoprotein are effective activators of macrophages, neutrophils and lymphocytes. We studied the effect of the lipopeptide N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]- (R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S)-lysyl-(S)-lysine [Pam3Cys-Ser-(Lys)4] on tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells, using anti-phosphotyrosine antibodies. Pam3Cys-Ser-(Lys)4 concentration-dependently stimulated tyrosine phosphorylation of 100/110 kDa and 60 kDa proteins and, to a lesser extent, of 55 kDa and 70/75 kDa proteins. Half-maximal and maximal effects were observed at concentrations of 1-6 and 5-50 micrograms/ml respectively. The lipopeptide-induced increase in phosphorylation was rapid and transient, with a peak response after 30-60 s. The lipopeptide (2S)-2-palmitoylamino-6-palmitoyloxymethyl-7-palmitoyloxy heptanoyl-Ser-(Lys)4 [Pam3Ahh-Ser-(Lys)4] was as potent as Pam3Cys-Ser(Lys)4, whereas (2S,6S)-2-palmitoylamino-6,7-bis(palmitoyloxy)heptanoyl++ +-Ser-(Lys)4 [Pam3Adh-Ser-(Lys)4] and Pam3Cys-Ser-Gly did not induce tyrosine phosphorylation. Lipopeptide-induced tyrosine phosphorylation was not affected by treatment of cells with pertussis toxin. Neither phorbol 12-myristate 13-acetate nor A23187 induced tyrosine phosphorylation in dibutyryl-cyclic-AMP-differentiated HL-60 cells. In HL-60 promyelocytes, Pam3Cys-Ser-(Lys)4 had no effect on tyrosine phosphorylation, whereas the lipopeptide also induced tyrosine phosphorylation in 1,25-dihydroxyvitamin-D3-differentiated HL-60 cells and in human neutrophils. These results show that lipopeptides are effective stimulators of tyrosine phosphorylation in mature human myeloid cells.
|Institutions:|| Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann formerly Prof. Seifert)|
|Cell Differentiation/drug effects||MESH|
|Electrophoresis, Polyacrylamide Gel||MESH|
|Virulence Factors, Bordetella/pharmacology||MESH|
|Subjects:||600 Technology > 615 Pharmacy|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||24 Jan 2012 08:04|
|Last Modified:||24 Jan 2012 12:58|