PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. Export

@article{citeulike:419077, abstract = {Activation of the transcription factor NF-kappaB after engagement of the T cell receptor (TCR) is important for T cell proliferation and activation during the adaptive immune response. Recent reports have elucidated a signaling pathway that involves the protein kinase C (PKC), the scaffold protein CARD11 (also called CARMA-1), the caspase recruitment domain (CARD)-containing protein Bcl10, and the paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the IkappaB kinase (IKK) complex. However, the events proximal to the TCR that initiate the activation of this signaling pathway remain poorly defined. We demonstrate that 3-phosphoinositide-dependent kinase 1 (PDK1) has an essential role in this pathway by regulating the activation of PKC and through signal-dependent recruiting of both PKC and CARD11 to lipid rafts. PDK1-associated PKC recruits the IKK complex, whereas PDK1-associated CARD11 recruits the Bcl10-MALT1 complex, thereby allowing activation of the IKK complex through Bcl10-MALT1-dependent ubiquitination of the IKK complex subunit known as NEMO (NF-kappaB essential modifier). Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells.}, address = {Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA.}, author = {Lee, K. Y. and D'Acquisto, F. and Hayden, M. S. and Shim, J. H. and Ghosh, S.}, citeulike-article-id = {419077}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1107107}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/308/5718/114}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/15802604}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=15802604}, comment = {reaction 87}, day = {1}, doi = {10.1126/science.1107107}, issn = {1095-9203}, journal = {Science}, keywords = {pkct, tcrmr}, month = {April}, number = {5718}, pages = {114--118}, posted-at = {2006-06-28 11:21:11}, priority = {5}, title = {PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation.}, url = {http://dx.doi.org/10.1126/science.1107107}, volume = {308}, year = {2005} }

TY - JOUR ID - citeulike:419077 L3 - citeulike-article-id:419077 N2 - Activation of the transcription factor NF-kappaB after engagement of the T cell receptor (TCR) is important for T cell proliferation and activation during the adaptive immune response. Recent reports have elucidated a signaling pathway that involves the protein kinase C (PKC), the scaffold protein CARD11 (also called CARMA-1), the caspase recruitment domain (CARD)-containing protein Bcl10, and the paracaspase (protease related to caspases) MALT1 as critical intermediates linking the TCR to the IkappaB kinase (IKK) complex. However, the events proximal to the TCR that initiate the activation of this signaling pathway remain poorly defined. We demonstrate that 3-phosphoinositide-dependent kinase 1 (PDK1) has an essential role in this pathway by regulating the activation of PKC and through signal-dependent recruiting of both PKC and CARD11 to lipid rafts. PDK1-associated PKC recruits the IKK complex, whereas PDK1-associated CARD11 recruits the Bcl10-MALT1 complex, thereby allowing activation of the IKK complex through Bcl10-MALT1-dependent ubiquitination of the IKK complex subunit known as NEMO (NF-kappaB essential modifier). Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells. IS - 5718 JF - Science SN - 1095-9203 AD - Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA. EP - 118 TI - PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. VL - 308 SP - 114 KW - pkct KW - tcrmr N1 - reaction 87 AU - Lee, KY AU - D'Acquisto, F AU - Hayden, MS AU - Shim, JH AU - Ghosh, S PY - 2005/04/01/ UR - http://dx.doi.org/10.1126/science.1107107 ER -