Protein Kinase Ctheta Focusing at the cSMAC Is a Consequence rather than Cause of TCR Signaling and Is Dependent on the MEK/ERK Pathway Export

@article{citeulike:4462631, abstract = {Correlation between protein kinase C{theta} focusing within the central supramolecular activation cluster (cSMAC) of the immunological synapse and optimal TCR/costimulatory receptor ligation was interpreted to imply that PKC{theta} focusing is required for productive signaling. However, this notion has been called into question and competing data suggest that the cSMAC contributes to receptor down-modulation. The observation that PKC{theta} focusing at the cSMAC is promoted by CD28 coligation, and also that it occurs late after proximal tyrosine phosphorylation events have been initiated, has led us to investigate an alternative possibility that PKC{theta} focusing might be a consequence rather than a cause of productive integrated signaling. Indeed, we found that inhibition of the downstream signaling molecules MEK and PI3K (but not of calcineurin, NF-{kappa}B, JNK, or p38 MAPK) significantly prevented the focusing of PKC{theta} at the cSMAC. It recently has been suggested that the cSMAC may be associated with TCR degradation and signal termination. Using MEK inhibition as a tool, we observed that absence of detectable PKC{theta} focusing had no significant effect on TCR down-modulation or duration of CD3{zeta} phosphorylation. Our results suggest that PKC{theta} focusing at the cSMAC occurs as a consequence of productive integrated downstream signaling at least at the level of MEK. If PKC{theta} focusing accurately reflects the cSMAC as a whole, then our data also argue against the cSMAC as being required for proximal TCR signal termination. 10.4049/jimmunol.0800897}, author = {Praveen, Kesavannair and Zheng, Yan and Rivas, Fabiola and Gajewski, Thomas F.}, citeulike-article-id = {4462631}, citeulike-linkout-0 = {http://dx.doi.org/10.4049/jimmunol.0800897}, citeulike-linkout-1 = {http://www.jimmunol.org/cgi/content/abstract/182/10/6022}, day = {15}, doi = {10.4049/jimmunol.0800897}, journal = {J Immunol}, keywords = {erk, pkctheta, synapse}, month = {May}, number = {10}, pages = {6022--6030}, posted-at = {2009-05-04 22:04:24}, priority = {2}, title = {Protein Kinase C{theta} Focusing at the cSMAC Is a Consequence rather than Cause of TCR Signaling and Is Dependent on the MEK/ERK Pathway}, url = {http://dx.doi.org/10.4049/jimmunol.0800897}, volume = {182}, year = {2009} }

TY - JOUR ID - citeulike:4462631 L3 - citeulike-article-id:4462631 N2 - Correlation between protein kinase C{theta} focusing within the central supramolecular activation cluster (cSMAC) of the immunological synapse and optimal TCR/costimulatory receptor ligation was interpreted to imply that PKC{theta} focusing is required for productive signaling. However, this notion has been called into question and competing data suggest that the cSMAC contributes to receptor down-modulation. The observation that PKC{theta} focusing at the cSMAC is promoted by CD28 coligation, and also that it occurs late after proximal tyrosine phosphorylation events have been initiated, has led us to investigate an alternative possibility that PKC{theta} focusing might be a consequence rather than a cause of productive integrated signaling. Indeed, we found that inhibition of the downstream signaling molecules MEK and PI3K (but not of calcineurin, NF-{kappa}B, JNK, or p38 MAPK) significantly prevented the focusing of PKC{theta} at the cSMAC. It recently has been suggested that the cSMAC may be associated with TCR degradation and signal termination. Using MEK inhibition as a tool, we observed that absence of detectable PKC{theta} focusing had no significant effect on TCR down-modulation or duration of CD3{zeta} phosphorylation. Our results suggest that PKC{theta} focusing at the cSMAC occurs as a consequence of productive integrated downstream signaling at least at the level of MEK. If PKC{theta} focusing accurately reflects the cSMAC as a whole, then our data also argue against the cSMAC as being required for proximal TCR signal termination. 10.4049/jimmunol.0800897 IS - 10 JF - J Immunol EP - 6030 TI - Protein Kinase C{theta} Focusing at the cSMAC Is a Consequence rather than Cause of TCR Signaling and Is Dependent on the MEK/ERK Pathway VL - 182 SP - 6022 KW - erk KW - pkctheta KW - synapse AU - Praveen, Kesavannair AU - Zheng, Yan AU - Rivas, Fabiola AU - Gajewski, Thomas PY - 2009/05/15/ UR - http://dx.doi.org/10.4049/jimmunol.0800897 ER -