Merlin Phosphorylation by p21-activated Kinase 2 and Effects of Phosphorylation on Merlin Localization

• Published in: The Journal of biological chemistry Vol. 277; no. 12; pp. 10394 - 10399
• Main Authors: Kissil, Joseph L., Johnson, Kristen C., Eckman, Matthew S., Jacks, Tyler
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-03-2002; American Society for Biochemistry and Molecular Biology
• Subjects: 3T3 Cells; Animals; Blotting, Western; cdc42 GTP-Binding Protein - metabolism; Cell Line; Mice; Mutation; Neurofibromin 2 - metabolism; p21-Activated Kinases; Phosphorylation; Plasmids - metabolism; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases - metabolism; Serine - chemistry; Serine - metabolism; Signal Transduction; Subcellular Fractions - metabolism; Swine; Time Factors; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M200083200

The Nf2 tumor suppressor gene product merlin is related to the membrane-cytoskeleton linker proteins of the band 4.1 superfamily, including ezrin, radixin, and moesin (ERMs). Merlin is regulated by phosphorylation in a Rac/cdc42-dependent fashion. We report that the phosphorylation of merlin at serine 518 is induced by the p21-activated kinase PAK2. This is demonstrated by biochemical fractionation, use of active and dominant-negative mutants of PAK2, and immunodepletion. By using wild-type and mutated forms of merlin and phospho-directed antibodies, we show that phosphorylation of merlin at serine 518 leads to dramatic protein relocalization.