Abstract
The muscle A-kinase anchoring protein (mAKAP) tethers cAMP-dependent enzymes to perinuclear membranes of cardiomyocytes. We now demonstrate that two alternatively spliced forms of mAKAP are expressed: mAKAPalpha and mAKAPbeta. The longer form, mAKAPalpha, is preferentially expressed in the brain. mAKAPbeta is a shorter form of the anchoring protein that lacks the first 244 amino acids and is preferentially expressed in the heart. The unique amino terminus of mAKAPalpha can spatially restrict the activity of 3-phosphoinositide-dependent kinase-1 (PDK1). Biochemical and genetic analyses demonstrate that simultaneous recruitment of PDK1 and ERK onto mAKAPalpha facilitates activation and release of the downstream target p90RSK. The assembly of tissue-specific signaling complexes provides an efficient mechanism to integrate and relay lipid-mediated and mitogenic activated signals to the nucleus.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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A Kinase Anchor Proteins
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism*
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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Cell Line
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Cloning, Molecular
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Organ Specificity / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA, Messenger / genetics
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Rats
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Ribosomal Protein S6 Kinases, 90-kDa / metabolism
Substances
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A Kinase Anchor Proteins
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Adaptor Proteins, Signal Transducing
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Akap6 protein, rat
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RNA, Messenger
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mAkap6 protein, mouse
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Pdpk1 protein, mouse
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Pdpk1 protein, rat
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases, 90-kDa
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Extracellular Signal-Regulated MAP Kinases
Associated data
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GENBANK/DQ233645
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GENBANK/DQ233646