Protein Kinase Cμ Regulation of the JNK Pathway Is Triggered via Phosphoinositide-dependent Kinase 1 and Protein Kinase Cε Export

@article{citeulike:6029196, abstract = {10.1074/jbc.M205299200 The protein kinase C (PKC)-related enzyme PKC\^{I}¼/PKD (protein kinase D) is activated by activation loop phosphorylation through PKC\^{I}·. Here we demonstrate that PKC\^{I}¼ is activated by the direct phosphorylation of PKC\^{I}µ. PKC\^{I}¼ colocalizes with PKC\^{I}µ in HEK293 and MCF7 cells as shown by confocal immunofluorescence analyses. PDK1, known as the upstream kinase for several PKC isozymes, associates intracellularly with PKC\^{I}µ and PKC\^{I}·. PKC\^{I}· is phosphorylated by PDK1 , leading to kinase activation as similarly reported for PKC\^{I}µ activation by PDK1. Coexpression of PDK1, PKC\^{I}µ and PKC\^{I}¼ in HEK293 cells results in PKC\^{I}¼ activation. In contrast, the coexpression of PDK1 and PKC\^{I}· with PKC\^{I}¼ does not activate PKC\^{I}· or consequently PKC\^{I}¼. PDK1/PKC\^{I}µ-triggered activation of PKC\^{I}¼ inhibits JNK, a downstream effector of PKC\^{I}¼, whereas upon transient expression of PDK1, PKC\^{I}·, and PKC\^{I}¼, JNK is not affected. These data implicate PKC\^{I}µ as the biologically important upstream kinase for PKC\^{I}¼ in HEK293 cells, regulating downstream effectors. Our results further indicate a PDK1/PKC\^{I}·/PKC\^{I}¼ controlled negative regulation of PKC\^{I}· kinase activity. In this study, we show that differentially activated kinase cascades involving PDK1 and novel PKC isotypes are responsible for the regulation of PKC\^{I}¼ activity and consequently inhibit the JNK pathway.}, author = {Br\~{A}¤ndlin, Ilona and Eiseler, Tim and Salowsky, R\~{A}¼diger and Johannes, Franz-Josef}, citeulike-article-id = {6029196}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M205299200}, citeulike-linkout-1 = {http://www.jbc.org/content/277/47/45451.abstract}, citeulike-linkout-2 = {http://www.jbc.org/content/277/47/45451.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/12223477}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=12223477}, day = {22}, doi = {10.1074/jbc.M205299200}, journal = {Journal of Biological Chemistry}, keywords = {jnk, pdk1, pkc, pkd}, month = {November}, number = {47}, pages = {45451--45457}, posted-at = {2009-10-28 22:05:33}, priority = {2}, title = {Protein Kinase C\^{I}¼ Regulation of the JNK Pathway Is Triggered via Phosphoinositide-dependent Kinase 1 and Protein Kinase C\^{I}µ}, url = {http://dx.doi.org/10.1074/jbc.M205299200}, volume = {277}, year = {2002} }

TY - JOUR ID - citeulike:6029196 L3 - citeulike-article-id:6029196 N2 - 10.1074/jbc.M205299200 The protein kinase C (PKC)-related enzyme PKCμ/PKD (protein kinase D) is activated by activation loop phosphorylation through PKCη. Here we demonstrate that PKCμ is activated by the direct phosphorylation of PKCε. PKCμ colocalizes with PKCε in HEK293 and MCF7 cells as shown by confocal immunofluorescence analyses. PDK1, known as the upstream kinase for several PKC isozymes, associates intracellularly with PKCε and PKCη. PKCη is phosphorylated by PDK1 , leading to kinase activation as similarly reported for PKCε activation by PDK1. Coexpression of PDK1, PKCε and PKCμ in HEK293 cells results in PKCμ activation. In contrast, the coexpression of PDK1 and PKCη with PKCμ does not activate PKCη or consequently PKCμ. PDK1/PKCε-triggered activation of PKCμ inhibits JNK, a downstream effector of PKCμ, whereas upon transient expression of PDK1, PKCη, and PKCμ, JNK is not affected. These data implicate PKCε as the biologically important upstream kinase for PKCμ in HEK293 cells, regulating downstream effectors. Our results further indicate a PDK1/PKCη/PKCμ controlled negative regulation of PKCη kinase activity. In this study, we show that differentially activated kinase cascades involving PDK1 and novel PKC isotypes are responsible for the regulation of PKCμ activity and consequently inhibit the JNK pathway. IS - 47 JF - Journal of Biological Chemistry EP - 45457 TI - Protein Kinase Cμ Regulation of the JNK Pathway Is Triggered via Phosphoinositide-dependent Kinase 1 and Protein Kinase Cε VL - 277 SP - 45451 KW - jnk KW - pdk1 KW - pkc KW - pkd AU - Brändlin, Ilona AU - Eiseler, Tim AU - Salowsky, Rüdiger AU - Johannes, Franz-Josef PY - 2002/11/22/ UR - http://dx.doi.org/10.1074/jbc.M205299200 ER -