TI <prot></prot> - Type II regulatory subunit dimerization determines the subcellular
     <prot></prot> localization of the <prot>cAMP-dependent protein kinase</prot>.
PG <prot></prot> - 21561-6
AB <prot></prot> - The <prot></prot> <prot>type II <prot>cAMP-dependent protein kinase</prot></prot> (<prot>PKA</prot>) <prot></prot> is localized to specific
     <prot></prot> subcellular environments through binding of dimeric regulatory subunits
      <prot></prot> (RII) <prot></prot> to anchoring proteins. Cytoskeletal localization occurs through <prot></prot> RII 
     <prot></prot> dimer interaction with the <prot></prot> <prot>PKA</prot> <prot></prot> substrate molecule <prot></prot> <prot>microtubule-associated
     <prot></prot> protein 2</prot> (<prot>MAP2</prot>) . <prot></prot> RII alpha <prot></prot> deletion mutants and <prot></prot> RII alpha/<prot>endonexin</prot> 
     <prot></prot> chimeras retained  <prot></prot> <prot>MAP2</prot>  <prot></prot> binding activity if they contained the first 79
     <prot></prot> residues of the molecule. Disruption of  <prot></prot> RII alpha  <prot></prot> dimerization always
     <prot></prot> prevented <prot>MAP2</prot> interaction because 1) RII delta 1-14 (an amino-terminal
     <prot></prot> deletion mutant lacking residues 1-14) was unable to bind <prot>MAP2</prot> or form
     <prot></prot> dimers, and 2) a modified RII alpha monomer including residues 1-14 did
     <prot></prot> not bind <prot>MAP2</prot>. Chimeric proteins containing the first 30 residues of RII
     <prot></prot> alpha fused to <prot>endonexin</prot> II formed dimers but did not bind <prot>MAP2</prot>. This
     <prot></prot> suggested other side-chains between residues 30-79 also participate in
     <prot></prot> <prot>MAP2</prot> interaction. Peptide studies indicate additional contact with <prot>MAP2</prot>
     <prot></prot> may occur through an acidic region (residues 68-82) close to the RII
     <prot></prot> autoinhibitor domain. Therefore, anchored <prot>PKA</prot> holoenzyme topology may
     <prot></prot> position the catalytic subunit and <prot>MAP2</prot> as to allow its preferential
     <prot></prot> phosphorylation upon kinase activation.
AD <prot></prot> - Vollum Institute for Advanced Biomedical Research, Portland, Oregon 97201.





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