title: A peptide-functionalized polymer as a minimal scaffold protein to enhance cluster formation in early T cell signal transduction.
abstract: In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline-rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N-(2-hydroxypropyl)methacrylamide polymer backbone. When added to GADS-containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross-linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling proteins.
authors: Department of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen (The Netherlands).
authors: J Joris
authors: JJ
authors: Witsenburg
authors: Michael D
authors: MD
authors: Sinzinger
authors: Oda
authors: O
authors: Stoevesandt
authors: Ivo R
authors: IR
authors: Ruttekolk
authors: Günter
authors: G
authors: Roth
authors: Merel J W
authors: MJ
authors: Adjobo-Hermans
authors: Roland
authors: R
authors: Brock
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000494:pharmacology; D011392:Proline / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C409587:GRAP2 protein, human; D010455:Peptides; D011109:Polymethacrylic Acids; C011533:Duxon; D011392:Proline
keywords: immunology; microcontact printing; multivalency; scaffold protein; signal transduction