title: Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and MEK1 and ERK2 to the actin cytoskeleton.
abstract: 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.
authors.affiliation: Cell Biology Programme, The Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1X8, Canada.
authors.forename: Rene E
authors.initials: RE
authors.lastname: Harrison
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Sikorski
authors.forename: Jan
authors.initials: J
authors.lastname: Jongstra
mesh_terms: D000199:Actins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors; D014162:Transfection
chemical_list: D000199:Actins; D001798:Blood Proteins; D002352:Carrier Proteins; C034037:F-actin-binding proteins; D007075:Immunoglobulin M; D047908:Intracellular Signaling Peptides and Proteins; C093604:LST1 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D005982:Glutathione Transferase; D019950:Mitogen-Activated Protein Kinase 1; D048369:MAP Kinase Kinase 1