PMID- 10212242 OWN - NLM STAT- MEDLINE DCOM- 19990603 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 18 DP - 1999 Apr 30 TI - Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. PG - 12626-31 AB - Mechanisms for selective targeting to unique subcellular sites play an important role in determining the substrate specificities of protein kinases. Here we show that stress-activated protein kinase-3 (SAPK3, also called ERK6 and p38gamma), a member of the mitogen-activated protein kinase family that is abundantly expressed in skeletal muscle, binds through its carboxyl-terminal sequence -KETXL to the PDZ domain of alpha1-syntrophin. SAPK3 phosphorylates alpha1-syntrophin at serine residues 193 and 201 in vitro and phosphorylation is dependent on binding to the PDZ domain of alpha1-syntrophin. In skeletal muscle SAPK3 and alpha1-syntrophin co-localize at the neuromuscular junction, and both proteins can be co-immunoprecipitated from transfected COS cell lysates. Phosphorylation of a PDZ domain-containing protein by an associated protein kinase is a novel mechanism for determining both the localization and the substrate specificity of a protein kinase. FAU - Hasegawa, M AU - Hasegawa M AD - Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. FAU - Cuenda, A AU - Cuenda A FAU - Spillantini, M G AU - Spillantini MG FAU - Thomas, G M AU - Thomas GM FAU - Buee-Scherrer, V AU - Buee-Scherrer V FAU - Cohen, P AU - Cohen P FAU - Goedert, M AU - Goedert M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Bungarotoxins) RN - 0 (Calcium-Binding Proteins) RN - 0 (Membrane Proteins) RN - 0 (Muscle Proteins) RN - 0 (Peptide Fragments) RN - 0 (syntrophin alpha1) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.- (Mitogen-Activated Protein Kinase 12) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Amino Acid Sequence MH - Animals MH - Bungarotoxins/metabolism MH - COS Cells MH - Calcium-Binding Proteins MH - Fluorescent Antibody Technique MH - Membrane Proteins/chemistry/*metabolism MH - Mitogen-Activated Protein Kinase 12 MH - *Mitogen-Activated Protein Kinases MH - Molecular Sequence Data MH - Muscle Proteins/chemistry/*metabolism MH - Muscle, Skeletal/enzymology/metabolism MH - Neuromuscular Junction/enzymology/metabolism MH - Peptide Fragments/chemistry/metabolism MH - Phosphorylation MH - Precipitin Tests MH - Protein Binding MH - Protein Kinases/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Substrate Specificity EDAT- 1999/04/23 00:00 MHDA- 1999/04/23 00:01 CRDT- 1999/04/23 00:00 PHST- 1999/04/23 00:00 [pubmed] PHST- 1999/04/23 00:01 [medline] PHST- 1999/04/23 00:00 [entrez] AID - 10.1074/jbc.274.18.12626 [doi] AID - S0021-9258(19)73397-3 [pii] PST - ppublish SO - J Biol Chem. 1999 Apr 30;274(18):12626-31. doi: 10.1074/jbc.274.18.12626.