PMID- 10480937 OWN - NLM STAT- MEDLINE DCOM- 19991013 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 38 DP - 1999 Sep 17 TI - Characterization of the targeting, binding, and phosphorylation site domains of an A kinase anchor protein and a myristoylated alanine-rich C kinase substrate-like analog that are encoded by a single gene. PG - 27201-10 AB - A novel Drosophila A kinase anchor protein, Drosophila A kinase anchor protein 200 (DAKAP200), is predicted to be involved in routing, mediating, and integrating signals carried by cAMP, Ca(2+), and diacylglycerol (Li, Z., Rossi, E. A., Hoheisel, J. D., Kalderon, D., and Rubin, C. S. (1999) J. Biol. Chem. 274, 27191-27200). Experiments designed to assess this hypothesis now (a) establish the function, boundaries and identity of critical amino acids of the protein kinase AII (PKAII) tethering site of DAKAP200; (b) demonstrate that residues 119-148 mediate binding with Ca(2+)-calmodulin and F-actin; (c) show that a polybasic region of DAKAP200 is a substrate for protein kinase C; (d) reveal that phosphorylation of the polybasic domain regulates affinity for F-actin and Ca(2+)-calmodulin; and (e) indicate that DAKAP200 is myristoylated and that this modification promotes targeting of DAKAP200 to plasma membrane. DeltaDAKAP200, a second product of the DAKAP200 gene, cannot tether PKAII. However, DeltaDAKAP200 is myristoylated and contains a phosphorylation site domain that binds Ca(2+)-calmodulin and F-actin. An atypical amino acid composition, a high level of negative charge, exceptional thermostability, unusual hydrodynamic properties, properties of the phosphorylation site domain, and a calculated M(r) of 38,000 suggest that DeltaDAKAP200 is a new member of the myristoylated alanine-rich C kinase substrate protein family. DAKAP200 is a potentially mobile, chimeric A kinase anchor protein-myristoylated alanine-rich C kinase substrate protein that may facilitate localized reception and targeted transmission of signals carried by cAMP, Ca(2+), and diacylglycerol. FAU - Rossi, E A AU - Rossi EA AD - Department of Molecular Pharmacology, Atran Laboratories, Albert Einstein College of Medicine, Bronx, New York 10461, USA. FAU - Li, Z AU - Li Z FAU - Feng, H AU - Feng H FAU - Rubin, C S AU - Rubin CS LA - eng GR - DK07513/DK/NIDDK NIH HHS/United States GR - GM07260/GM/NIGMS NIH HHS/United States GR - GM22792/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (A Kinase Anchor Proteins) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Akap200 protein, Drosophila) RN - 0 (Carrier Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Proteins) RN - 125267-21-2 (Myristoylated Alanine-Rich C Kinase Substrate) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.13 (Protein Kinase C) RN - SY7Q814VUP (Calcium) SB - IM MH - A Kinase Anchor Proteins MH - *Adaptor Proteins, Signal Transducing MH - Amino Acid Sequence MH - Animals MH - Calcium/metabolism MH - Carrier Proteins/genetics/*metabolism MH - Chickens MH - Cyclic AMP/metabolism MH - *Drosophila Proteins MH - Drosophila melanogaster MH - *Intracellular Signaling Peptides and Proteins MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Microscopy, Fluorescence MH - Molecular Sequence Data MH - Mutagenesis, Site-Directed MH - Myristoylated Alanine-Rich C Kinase Substrate MH - Peptide Mapping MH - Phosphorylation MH - Protein Kinase C/genetics/*metabolism MH - Proteins/genetics/*metabolism MH - Signal Transduction MH - Structure-Activity Relationship EDAT- 1999/09/10 00:00 MHDA- 1999/09/10 00:01 CRDT- 1999/09/10 00:00 PHST- 1999/09/10 00:00 [pubmed] PHST- 1999/09/10 00:01 [medline] PHST- 1999/09/10 00:00 [entrez] AID - 10.1074/jbc.274.38.27201 [doi] AID - S0021-9258(19)55144-4 [pii] PST - ppublish SO - J Biol Chem. 1999 Sep 17;274(38):27201-10. doi: 10.1074/jbc.274.38.27201.