title: Optimization of the cellular import of functionally active SH2-domain-interacting phosphopeptides.
abstract: Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcgamma receptor IIb and a motif of the Grb2-associated binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into B cells. We found octanoyl-Arg(8) to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and time-dependent manner.
authors.affiliation: Department of Immunology, Eötvös Loránd University, Pázmány Péter s. 1c, 1117 Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Kertész
authors.forename: G
authors.initials: G
authors.lastname: Váradi
authors.forename: G K
authors.initials: GK
authors.lastname: Tóth
authors.forename: R
authors.initials: R
authors.lastname: Fajka-Boja
authors.forename: E
authors.initials: E
authors.lastname: Monostori
authors.forename: G
authors.initials: G
authors.lastname: Sármay
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D020816:Amino Acid Motifs; D001402:B-Lymphocytes / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000378:metabolism*; D006801:Humans; D010539:Permeability; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D015398:Signal Transduction; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C098587:GAB1 protein, human; D010748:Phosphopeptides; D010750:Phosphoproteins; D019000:Phosphotyrosine