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

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 PKCbetaI and expression of B-LSP1, an LSP1 truncate containing the PKCbetaI binding residues, inhibits ...
anti-IgM-induced translocation of PKCbetaI to the plasma membrane and anti-IgM-induced activation of ERK2. To understand the role of LSP1 in the regulation of PKCbetaI-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 PKCbetaI 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, PKCbetaI and LSP1 and are activated by anti-IgM in a PKCbetaI-dependent manner.
Mesh Terms:
Actins, Blood Proteins, Carrier Proteins, Cell Line, Cell Line, Tumor, Cell Membrane, Cytoskeleton, Glutathione Transferase, Humans, Immunoglobulin M, Immunoprecipitation, Leukocytes, Lymphoma, B-Cell, MAP Kinase Kinase 1, MAP Kinase Signaling System, Membrane Proteins, Microfilament Proteins, Microscopy, Confocal, Mitogen-Activated Protein Kinase 1, Protein Binding, Time Factors, Transfection
J. Cell. Sci.
Date: Apr. 15, 2004
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