CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy
J. Clin. Invest. Johannes Backs, et al. 116:1853 doi:10.1172/JCI27438 [
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Figure 2Regulation of CaMKII subcellular localization. (
A) COS cells were transfected with CaMKIIδB-WT, CaMKIIδB-T287D, and CaMKIIδB-T287D/S332A. In contrast to the WT kinase, CaMKIIδB-T287D localized predominantly to the cytosol. Substitution of S332 rendered CaMKIIδB-T287D constitutively active and nuclear. (
B) COS cells were cotransfected with CaMKIIδB-T287D/S332A and HDAC4 or HDAC5. Note that only HDAC4 was exported in response to the double CaMKIIδB mutant and colocalized with the kinase. (
C and
D) COS cells were first transfected with the indicated CaMKIIδB mutants and 12 hours later with HDAC4. Twelve hours after transfection with HDAC4, cells were treated for another 4 hours either with 1 nM leptomycin B (lower panel) or the vehicle ethanol (upper panel). Note that with leptomycin B, HDAC4 only accumulates in the nucleus in the presence of CaMKIIδB-T287D/S332A, which is active and nuclear, but not in the presence of CaMKIIδB-T287D or CaMKIIδB-T287D/K328,329N, which are active and cytosolic. (
A–
C) Representative images. Magnification, ×40. (
D) Quantitative analysis of experiment shown in
C.