Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes.

Like phosphorylation, acetylation of lysine residues within a protein is considered a biologically relevant modification that controls the activity of target proteins. During stress of cells, massive protein acetylation takes place. Here, we show that p38 mitogen-activated protein kinase (MAPK), which controls many biological functions during stress, is reversibly acetylated by PCAF/p300 and HDAC3. We identified two acetylated lysine residues, K152 and K53, located in the substrate binding domain and in the ATP-binding pocket of p38, respectively. Acetylation of lysine 53 enhanced the activity of p38 by increasing its affinity for ATP binding. The enhanced acetylation and activation of p38 were found to be in parallel with reduced intracellular ATP levels in cardiomyocytes under stress, as well as in vivo models of cardiac hypertrophy. Thus, our data show, for the first time, that p38 activity is critically regulated by, in addition to phosphorylation, reversible acetylation of a lysine residue, which is conserved in other kinases, implying the possibility of a similar mechanism regulating their activity.

Pubmed ID: 21444723 RIS Download

Mesh terms: Acetylation | Acetyltransferases | Adenosine Triphosphate | Animals | Cells, Cultured | HEK293 Cells | HeLa Cells | Histone Deacetylases | Humans | Hypertrophy | Mass Spectrometry | Mice | Myocytes, Cardiac | Protein Processing, Post-Translational | Rats | Stress, Physiological | p300-CBP Transcription Factors | p38 Mitogen-Activated Protein Kinases

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: HL-83423
  • Agency: NHLBI NIH HHS, Id: K99 HL098366
  • Agency: NHLBI NIH HHS, Id: K99 HL098366-01
  • Agency: NHLBI NIH HHS, Id: K99 HL098366-02
  • Agency: NHLBI NIH HHS, Id: K99HL098366
  • Agency: NHLBI NIH HHS, Id: R00 HL098366
  • Agency: NHLBI NIH HHS, Id: R01 HL-77788

BioGRID (Data, Interactions)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.