title: A dipalmitoyl peptide that binds SH3 domain, disturbs intracellular signal transduction, and inhibits tumor growth in vivo.
abstract: The Src homology 3 (SH3) domain plays a crucial role in protein-protein interactions during intracellular signal transduction. Blocking the SH3-mediated protein binding may inhibit the corresponding signal transduction, and thus, block the cellular functions. In this study, a peptide that specifically binds to SH3 domain could be introduced into the intracellular region when the peptides were conjugated with dipalmitic acid and appeared to disturb intracellular signaling. The dipalmitoyl peptide appeared to inhibit the phosphorylation of ZAP-70, Lck, and T-cell antigen receptor zeta in Jurkat. Mobilization of the intracellular free calcium induced by anti-CD3 antibody was reduced after treatment with the dipalmitoyl peptide. It was also observed that the dipalmitoyl peptide inhibited cancer cell growth both in vitro and in vivo. These results suggest that the dipalmitoyl peptide that presumably disturbs SH3-mediated signal transduction may have a potent anti-proliferative activity, which would be useful as a potential anti-tumor agent.
authors.affiliation: College of Pharmacy and Division of Molecular Life Sciences, Ewha Womans University, 11 Daehyundong, Seoul, Republic of Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Jeong Hyeok
authors.initials: JH
authors.lastname: Hyeok Yoon
authors.forename: Mihyung
authors.initials: M
authors.lastname: Kim
authors.forename: Sujin
authors.initials: S
authors.lastname: Roh
authors.forename: Yeon-Sook
authors.initials: YS
authors.lastname: Lee
authors.forename: Baik-Lin
authors.initials: BL
authors.lastname: Seong
authors.forename: Kilhyoun
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004735:Energy Transfer; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010169:Palmitic Acids / Q000378:metabolism* / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains / Q000235:genetics*
chemical_list: D005456:Fluorescent Dyes; D008565:Membrane Proteins; D010169:Palmitic Acids; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C054979:antigen T cell receptor, zeta chain; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse; D002118:Calcium