You are currently viewing the editor's summary.
View Full TextLog in to view the full text
AAAS login provides access to Science for AAAS members, and access to other journals in the Science family to users who have purchased individual subscriptions.
Register for free to read this article
As a service to the community, this article is available for free. Existing users log in.
More options
Download and print this article for your personal scholarly, research, and educational use.
Buy a single issue of Science for just $15 USD.
Controlling signaling through clustering
Several cell surface receptors require the multidomain protein CIN85 for signaling. Kühn et al. elucidated its mode of action in B lymphocytes in which CIN85 associates with the adaptor protein SLP-65, which transmits activation signals from the B cell receptor (BCR). NMR spectroscopy and X-ray crystallography showed that CIN85 formed a stable trimer through its C-terminal, coiled-coil domain. The SH3 domains of CIN85 recruited multiple SLP-65 molecules that in turn bound to other CIN85 trimers, resulting in the formation of large CIN85–SLP-65 signaling clusters. Manipulating the oligomerization state of SLP-65 affected the efficiency of BCR signaling, which suggests that CIN85 sets the threshold for B cell activation by controlling the size of SLP-65 signaling clusters.