Since PALS1 nucleates a ternary complex containing CRB3 and PATJ, and further binds PAR6 to maintain cell polarity [3, 20, 21] , their contribution to TCR-mediated NF-kB was evaluated. Similarly to PALS1, mRNA for PATJ, CRB3, PAR6, were efficiently detected by RT-PCR ( Figure 5A ). The same hold true for the unrelated cell polarity protein SCRIB ( Figure 5A ). siRNA-based knockdown of PALS1 and CRB3 significantly decreased NF-kB activation in cells treated by antibodies against CD3 and CD28, or with a mixture of PMA and ionomycin. Although less dramatic, similar results were observed with PAR6 or PATJ knockdown. By contrast, NF-kB was normally activated in the absence of SCRIB ( Figure 5B ). In agreement, IkBa phosphorylation was diminished in lysates from CRB3-depleted cells, and to a lesser extent from PATJ-or PAR6-siRNA transfected cells, and not from SCRIB-depleted cells. Again, ERK phosphorylation occurred normally ( Figure 5C , D, E, and F). Altogether, our data suggest that PALS1 implication in the TCR-NF-kB pathway is inextricably linked to its cell polarity partners.