• Mohammad Saifur Rohman Laboratorium Biokimia FK Unibraw Malang



Muscle A-Kinase Anchoring Protein (mAKAP) is an A-kinase anchoring protein (AKAP) which targets cAMP-dependent protein kinase(PKA) to the nuclear envelope. mAKAP not only binds to PKA, but also to the ryanodine receptor (RyR2) and the rolipram-inhibitedcAMP-specific phosphodiesterase (PDE4D3). Amino acid sequence analysis revealed that mAKAP possesses LXCXE andFYDYSYL, the consensus-binding domain of pRB and CBP/p300, respectively. pRB and CBP/p300 are known as a key componentsin cardiomyocyte differentiation processes. Northern blot analysis revealed that mAKAP was expressed in a 13 day old rat heart andits expression increased by 15 days of age when cardiomyocytes reveal a terminal differentiation phenotype. In culturedcardiomyocytes mAKAP was expressed in differentiated but not undifferentiated. Accordingly, mAKAP may play a role in the terminaldifferentiation process through pRB-CBP/p300 functions. Furthermore, we observed mAKAP expression in old mdx heart, a mousemodel of Duchenne muscular dystrophy, compared to control mice. In the control heart, mAKAP transcripts were detected at 6-, 20-,64- and 76-weeks of age. However, mAKAP expression significantly appeared only in 64- and 76-week old mdx hearts. DelayedmAKAP expression in mdx may contribute to impaired function of pRB, CBP/p300, cAMP and Ca2+ complex.Key words: mAKAP, domain architecture, terminal differentiation, pRB, CBP/p300, mdx.


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