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.

Genomic regions associated with host response to porcine reproductive and respiratory syndrome vaccination and co-infection in nursery pigs

“…Interestingly, this SNP (WU_10.2_5_5693454) is located within the growth factor receptor-bound protein 2 ( GRB2 )-reltated adaptor protein 2 gene in pigs, also known as GRB2-related adaptor downstream of Shc (GADS) . In humans, GADS is involved in the formation of the T cell receptor complex [ 33 ] and has a known role in T cell development and signaling [ 34 ]. However, there was no evidence that this SNP was significantly associated with any of the VL traits.…”