Non-overlapping functions of Nck1 and Nck2 adaptor proteins in T cell activation

26.03.2014

Ngoenkam J, Paensuwan P, Preechanukul K, Khamsri B, Yiemwattana I, Beck-García E, Minguet S, Schamel WW, Pongcharoen S

Cell Commun Signal. 2014 Mar 26;12:21

Cell Commun Signal.         online article

Together with the grop of Sutatip Pongchaeron, Thailand, we studied the role of the adaptor proteins Nck1 and Nck2 in human T cells. There are two isoforms, Nck1 and Nck2, that are downstream of the T cell antigen receptor (T)CR that each contain three SH3 and one SH2 domains. Using specific shRNAs we down-regulated the expression of Nck1 or Nck2 in the human Jurkat T cell line. We found that down-regulation of Nck1 impaired TCR-induced activation of Erk MAPK pathway, activation of the transcription factors AP-1 and NFAT and subsequently, IL-2 and CD69 expression. In contrast, down-regulation of Nck2 hardly changed these activation read-outs. Hence, in contrast to Nck2, Nck1 is a positive regulator for TCR-induced T cell activation. Furthermore, we show that neither Nck isoform is upstream of the p38 MAPK pathway or of Ca2+influx as induced by TCR triggering. In conclusion, Nck1 and Nck2 have non-redundant roles in human T cell activation in contrast to murine T cells where these isoforms might be redundant.