the rate of nf-κb nuclear translocation is regulated by pka and a kinase interacting protein 1nf-κb核易位率受pka激酶相互作用蛋白1.pdfVIP

The Rate of NF-kB Nuclear Translocation Is Regulated by PKA and A Kinase Interacting Protein 1 1. 2. 3 2 2,3,4 Charles C. King , Mira Sastri , Philip Chang , Juniper Pennypacker , Susan S. Taylor * 1 Department of Pediatrics, University of California San Diego, La Jolla, California, United States of America, 2 Department of Pharmacology, University of California San Diego, La Jolla, California, United States of America, 3 Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, United States of America, 4 The Howard Hughes Medical Institute, University of California San Diego, La Jolla, California, United States of America Abstract The mechanism of PKAc-dependent NF-kB activation and subsequent translocation into the nucleus is not well defined. Previously, we showed that A kinase interacting protein 1 (AKIP1) was important for binding and retaining PKAc in the nucleus. Since then, other groups have demonstrated that AKIP1 binds the p65 subunit of NF-kB and regulates its transcriptional activity through the phosphorylation at Ser 276 by PKAc. However, little is known about the formation and activation of the PKAc/AKIP1/p65 complex and the rate at which it enters the nucleus. Initially, we found that the AKIP1 isoform (AKIP 1A) simultaneously binds PKAc and p65 in resting and serum starved cells. Using peptide arrays, we refined the region of AKIP 1A binding on PKAc and mapped the non-overlapping regions on AKIP 1A where PKAc and p65 bind. A peptide to the amino-terminus of PKAc (CAT 1-29) was generated to specifically disrupt the interaction between AKIP 1A and PKAc to study nuclear import of the complex. The rate of p65 n