http://mend.endojournals.org/cgi/content/full/24/5/941#T1
Michael and this same group previously published a paper looking at the effect of cdk5 signaling on GR phosphorylation in neurons. Now they extend their study to MR and the effect of cdk5 on its transcriptional activity. In the process of identifying the phospho-sites induced by cdk5 on MR, they also show that cdk5 induces hGR phosphorylation by mass spec at S267 (one of the same BDNF induced phospho-sites that we identified in our lab).
This paper is not particularly innovative but they do "good" science to address the molecular affects of cdk5 on MR and GR with relevance to action in the nervous system.
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It is interesting that CDK5 modulates both GR and MR in such similar ways, yet GR and MR impose opposite influences on BDNF expression. Besides showing that CDK5 inhibitor and siRNA abolished the effect on BDNF, I think including data of phosphorylation deficient mutants can further substantiate the point. In addition, the mutants can also be utilized along with GR to study the combinatorial regulation on BDNF.
ReplyDeleteChaowei, do you mean a kinase dead CDK5, because in Figure 3 they do look at the effect on transcriptional activity of mutating the residues on MR that are phosphorylated by CDK5? I think that only the triple mutant is convincing because the single mutations all alter aldosterone-mediated activation (the minus CDK5 bars in Fig 3B p947).
ReplyDeleteMarcus, I was going to ask if the human GR residue phosphorylated by CDK5 is S287 in rat. That's cool. I am sure you already knew this, but based in experiments presented in Fig 4, it also looks like you do not want to treat too long with Dex (more than 6h) or with too high of a concentration of Dex because it can negatively feedback on BDNF.