Previous studies had demonstrated that mastoparan(MP), a peptide derived from wasp venom with amphipathic properties, could potentially stimulate G-protein mediated signalling. It was also known that MP could disrupt membrane structure and alter the activity of certain phospholipases. To determine the structural requirements for disruption of membranes and for alteration of G-protein function, we constructed several analogs of the peptide and characterized them using Swiss 3T3 cell membranes. The effects of these peptides were measured on i) G-protein-mediated stimulation of phospholipase-C activity by GTPgamma and bombesin and ii) the membrane enzyme activities Ca2+-activated phospholipase-C and Na,K-ATPase. MP strongly inhibited all the above activities and caused membrane permeabilization. Substitution of one Lys residue by Gly at either the N- or C- terminal of the MP molecule resulted in peptides which selectively inhibited G-protein-stimulated phospholipase-C with no or slight membrane- perturbing effects. Introduction af additional Lys residues to MP led to the opposite effect. Thus, G-protein modulating and membrane-disrupting actions of MP appear to be not necessarily linked, and may be separated.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CM007312-03
Application #
3752420
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Division of Cancer Treatment
Department
Type
DUNS #
City
State
Country
United States
Zip Code