P110A unique CaMKII betaisoform and anchoring protein alphaKAP assemble with the Tyrosine kinase signaling complex in myocardium

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Abstract

aKAP is a Kinase Anchoring Protein derived from the CaMKIIa gene. aKAP is expressed in various tissue including muscle and brain. Cardiac tissue is shown to have a predominance of CaMKII dB and dC isoforms while a 73 kDa CaMKIIb4 isoform that is generated by alternative splicing of the CaMKIIb gene is also expressed in myocardium and muscle. The CaMKIIb4 isoform differs from the ubiquitous CaMKIIb isoform by the presence of three exons encoding three proline rich repeats in the C-terminal association domain. The proline rich motifs in CaMKIIb4 were found to directly bind SH3 domains and immunoprecipitation assays indicated the presence of Grb-2 and c-Src in the CaMKIIb4 complex. A direct interaction of aKAP with CaMKIIb4 could target the enzyme to subcellular membranes including the sarcoplasmic reticulum (SR). Furthermore, aKAP can associate with SERCA2a and target CaMKIIb4 and promote phosphorylation of phospholamban and the ryanodine receptor. These data suggest that aKAP via it's interactions with the unique CaMKIIb4 may serve to modulate calcium transport and integrate calcium signals with SH3 domain containing proteins at the SR.

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