A novel PKC-regulated mechanism controls CD44-ezrin association and directional cell motility

J W Legg; C A Lewis; M Parsons; T Ng; C M Isacke

doi:10.1038/ncb797

A novel PKC-regulated mechanism controls CD44-ezrin association and directional cell motility

J W Legg, C A Lewis, M Parsons, T Ng, C M Isacke

Research output: Contribution to journal › Article › peer-review

212 Citations (Scopus)

Abstract

The dynamic assembly and disassembly of membrane-cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.

Original language	English
Pages (from-to)	399 - 407
Number of pages	9
Journal	Nature Cell Biology
Volume	4
Issue number	6
DOIs	https://doi.org/10.1038/ncb797
Publication status	Published - 2002

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abstract = "The dynamic assembly and disassembly of membrane-cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.",

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AU - Lewis, C A

AU - Parsons, M

AU - Ng, T

AU - Isacke, C M

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AB - The dynamic assembly and disassembly of membrane-cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.

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JO - Nature Cell Biology

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A novel PKC-regulated mechanism controls CD44-ezrin association and directional cell motility

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