Disease relevance of Akap6

• We now extend this observation and show mAKAP is important for adrenergic-mediated hypertrophy [1].

High impact information on Akap6

• Now we demonstrate that the muscle-selective A-kinase anchoring protein, mAKAP, maintains a cAMP signaling module, including PKA and the rolipram-inhibited cAMP-specific phosphodiesterase (PDE4D3) in heart tissues [2].
• Targeting of protein kinase A by muscle A kinase-anchoring protein (mAKAP) regulates phosphorylation and function of the skeletal muscle ryanodine receptor [3].
• The muscle AKAP, mAKAP, co-localizes with the sarcoplasmic reticulum Ca2+ release channel or ryanodine receptor (RyR) [3].
• The mAKAP complex participates in the induction of cardiac myocyte hypertrophy by adrenergic receptor signaling [1].
• These data reveal a novel function of the mAKAP complex involving the integration of cAMP and Ca2+ signals that promote myocyte hypertrophy [1].

Biological context of Akap6

• Through the direct binding of the nesprin-1alpha amino-terminal dimerization domain to the third mAKAP spectrin repeat, nesprin-1alpha targets mAKAP to the nuclear envelope [4].
• Experiments utilizing inhibition of the ryanodine receptor, RNA interference of mAKAP expression and replacement of endogenous mAKAP with a mutant form that does not bind to protein kinase A demonstrate that the mAKAP complex contributes to pro-hypertrophic signaling [1].

Anatomical context of Akap6

• Analysis of mAKAP-green fluorescent protein (GFP) fusion constructs revealed that nuclear membrane targeting is conferred by two regions of the protein, between residues 772-915 and 915-1065, which contain spectrin-like repeat sequences [5].
• In turn, overexpression of these spectrin repeat domains in myocytes can displace mAKAP from nesprin-1alpha [4].
• Nesprin-1alpha contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope [4].

Other interactions of Akap6

• They were the microtubule-associated protein 1A, protein-tyrosine phosphatase zeta precursor (phosphacan), and protein kinase A anchoring protein 6 [6].

References