Research ArticleTCR Signaling

Inhibition of T cell activation and function by the adaptor protein CIN85

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Sci. Signal.  05 Feb 2019:
Vol. 12, Issue 567, eaav4373
DOI: 10.1126/scisignal.aav4373

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Thou shalt not CIN

The ubiquitously expressed adaptor protein CIN85 has distinct roles in different cell types. This adaptor inhibits the activation of the receptor tyrosine kinases EGFR and PDGFR but promotes B cell receptor signaling. To determine its function in T cells, Kong et al. compared the activation of mouse T cells lacking CIN85 or the highly related adaptor CD2AP. Only loss of CIN85 augmented T cell growth and IL-2 production. CIN85 associated with the inhibitory phosphatase Sts-2 and promoted its recruitment to T cell receptor microclusters after activation. These data define a previously unknown inhibitory interaction, which could be targeted to augment T cell function in cancer and immunity.