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The adaptor protein CrkII regulates T cell adhesion by recruiting the guanine nucleotide exchange factor C3G, an activator of Rap1. Subsequently, Rap1 stimulates the integrin LFA-1, which leads to T cell adhesion and interaction with antigen-presenting cells (APCs). The adhesion of T cells to APCs is critical for their proper function and education. The interface between the T cell and the APC is known as the immunological synapse. It is characterized by the specific organization of proteins that can be divided into central supramolecular activation clusters (c-SMACs) and peripheral SMACs (p-SMACs). Through total internal reflection fluorescence (TIRF) microscopy and experiments with supported lipid bilayers, we determined that activated Rap1 was recruited to the immunological synapse and localized to the p-SMAC. C3G and the active (dephosphorylated) form of CrkII also localized to the same compartment. In contrast, inactive (phosphorylated) CrkII was confined to the c-SMAC. Activation of CrkII and its subsequent movement from the c-SMAC to the p-SMAC depended on the phosphatase SHP-1, which acted downstream of the T cell receptor. In the p-SMAC, CrkII recruited C3G, which led to Rap1 activation and LFA-1-mediated adhesion of T cells to APCs. Functionally, SHP-1 was necessary for both the adhesion and migration of T cells. Together, these data highlight a signaling pathway in which SHP-1 acts through CrkII to reshape the pattern of Rap1 activation in the immunological synapse.

Original publication




Journal article


Sci Signal

Publication Date





Adaptive Immunity, Animals, Cell Adhesion, GTPase-Activating Proteins, Guanine Nucleotide-Releasing Factor 2, HEK293 Cells, Humans, Immunological Synapses, Jurkat Cells, Lymphocyte Activation, Lymphocyte Function-Associated Antigen-1, Mice, Mice, Transgenic, Phosphorylation, Primary Cell Culture, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Proto-Oncogene Proteins c-crk, Receptors, Antigen, T-Cell, Single-Cell Analysis, T-Lymphocytes