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First published online April 16, 2004
doi: 10.1242/10.1242/jcs.00955

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Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and MEK1 and ERK2 to the actin cytoskeleton

¹ Cell Biology Programme, The Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1X8, Canada
² Toronto Western Research Institute, Cell and Molecular Biology Division, University Health Network, and Department of Immunology, University of Toronto, Toronto, Ontario, M5T 2S8, Canada

^* Author for correspondence (e-mail: jongstra{at}uhnres.utoronto.ca)

Accepted 28 October 2003

The identification and characterization of scaffold and targeting proteins of the ERK/MAP kinase pathway is important to understand the function and intracellular organization of this pathway. The F-actin binding protein leukocyte-specific protein 1 (LSP1) binds to PKCßI and expression of B-LSP1, an LSP1 truncate containing the PKCßI binding residues, inhibits anti-IgM-induced translocation of PKCßI to the plasma membrane and anti-IgM-induced activation of ERK2. To understand the role of LSP1 in the regulation of PKCßI-dependent ERK2 activation, we investigated whether LSP1 interacts with ERK/MAP kinase pathway components and targets these proteins to the actin cytoskeleton. We show that LSP1 associates with the ERK scaffold protein KSR and with MEK1 and ERK2. LSP1-associated MEK1 is activated by anti-IgM treatment and this activation is inhibited by expression of B-LSP1, suggesting that the activation of LSP1-associated MEK1 is PKCßI dependent. Confocal microscopy showed that LSP1 targets KSR, MEK1 and ERK2 to peripheral actin filaments. Thus our data show that LSP1 is a cytoskeletal targeting protein for the ERK/MAP kinase pathway and support a model in which MEK1 and ERK2 are organized in a cytoskeletal signaling complex together with KSR, PKCßI and LSP1 and are activated by anti-IgM in a PKCßI-dependent manner.

Key words: LSP1, Targeting, Actin cytoskeleton, ERK2, MAP kinase, B-lymphoma

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