Figure 6.

Our model of the role of actin polymerization in promoting non‐catalytic region of tyrosine kinase (Nck) ‐binding to the ligand‐/antibody‐engaged T‐cell receptor (TCR). Engagement of the TCR first leads to actin remodeling (1); this might be caused by fast and very‐low‐level downstream signaling. The polymerized actin promotes binding of the SH3·1(Nck) domain to the proline‐rich sequence (light blue box) in the CD3ε (2). This transient and weak interaction promotes the phosphorylation of CD3, possibly due to the interaction of Nck with Lck (3). If the second immunoreceptor‐tyrosine based activation motif (ITAM) tyrosine of CD3ε is phosphorylated, Nck can bind using its SH3·1 and SH2 domains in a cooperative manner (4). This binding mode is strong and together with ζ chain‐associated protein kinase of 70 000 MW (ZAP70) binding to doubly phosphorylated ITAMs leads to T‐cell activation (left panel). If actin polymerization is blocked, the following downstream events do not occur in an efficient manner (right panel).