Regulation and Function of the CD3γ DxxxLL Motif: A Binding Site for Adaptor Protein-1 and Adaptor Protein-2 in Vitro

• DOI: 10.1083/jcb.138.2.271
• Publication Date: 2002-07-26T16:47:50Z
• Authors: Jes Dietrich; Jesper Kastrup; Bodil L. Nielsen; Niels Ødum; Carsten Geisler
• Keywords: Internalization

Several receptors are downregulated by internalization after ligand binding. Regulation of T cell receptor (TCR) expression is an important step in activation, desensitization, and tolerance induction. One way cells regulate TCR phosphorylation/dephosphorylation the subunit clusters differentiation (CD)3γ. Thus, phosphorylation CD3γ serine 126 (S126) causes a downregulation TCR. In this study, we have analyzed motif three different systems parallel: context complete multimeric TCR; monomeric CD4/CD3γ chimeras; vitro binding peptides to clathrin-coated vesicle adaptor proteins (APs). We find that D127xxxLL131/132 sequence represents one united for both AP-1 AP-2, functions as active sorting CD4/ molecules independently S126. An acidic amino acid required at position 127 leucine (L) 131, whereas requirements 132 more relaxed. The spacing between aspartic (D127) L131 crucial function vivo AP vitro. Furthermore, provide evidence indicating S126 induces conformational change exposes DxxxLL Exposure increase rate demonstrate leads impairment signaling. On basis present results, propose existence least types L-based motifs.