A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95.

Using a yeast interaction screen to search for proteins that interact with cyclin D3 in thyroid gland, we identified the cAMP-dependent AKAP95 (protein kinase A-anchoring protein 95). AKAP95 is a scaffolding protein that primarily co-fractionates with the nuclear matrix, whereas a minor fraction associates with chromatin in interphase cells. In ...
co-transfected Chinese-hamster ovary cells, AKAP95 strongly interacted with the three D-type cyclins, but not with CDK4 (cyclin-dependent kinase 4) or with p27kip1. CDK4 displaced the interaction between cyclin D3 and AKAP95, suggesting that AKAP95 could not be the elusive bridging adaptor between D-type cyclins and CDK4 or play a role in the regulation of cyclin D3-CDK4 activity. Interaction between endogenous AKAP95 and cyclin D3 or cyclin D1 was detected in canine thyrocytes, human fibroblasts and NIH-3T3 cells. As both AKAP95 and cyclins D were recently reported to associate with minichromosome maintenance proteins [Eide, Tasken, Carlson, Williams, Jahnsen, Tasken and Collas (2003) J. Biol. Chem. 278, 26750-26756; Gladden and Diehl (2003) J. Biol. Chem. 278, 9754-9760], we hypothesize that the interaction between AKAP95 and D-type cyclins might serve to facilitate the emerging regulatory role of cyclin D-CDK4 in the formation of the prereplication complex at the DNA replication origins.
Mesh Terms:
A Kinase Anchor Proteins, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, CHO Cells, Carrier Proteins, Cells, Cultured, Cloning, Molecular, Cricetinae, Cricetulus, Cyclic AMP-Dependent Protein Kinases, Cyclin D, Cyclin D3, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinases, Cyclins, Dogs, Humans, Molecular Sequence Data, Proteins, Proto-Oncogene Proteins, Sequence Homology, Amino Acid, Two-Hybrid System Techniques
Biochem. J.
Date: Mar. 01, 2004
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