Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Leukocyte-specific protein 1 targets the ERK/MAP kinase scaffold protein KSR and MEK1 and ERK2 to the actin cytoskeleton. 1509 Jun