The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3.
The MLK (mixed lineage) ser/thr kinases are most closely related to the MAP kinase kinase kinase family. In addition to a kinase domain, MLK1, MLK2 and MLK3 each contain an SH3 domain, a leucine zipper domain and a potential Rac/Cdc42 GTPase-binding (CRIB) motif. The C-terminal regions of the proteins are ... essentially unrelated. Using yeast two-hybrid analysis and in vitro dot-blots, we show that MLK2 and MLK3 interact with the activated (GTP-bound) forms of Rac and Cdc42, with a slight preference for Rac. Transfection of MLK2 into COS cells leads to strong and constitutive activation of the JNK (c-Jun N-terminal kinase) MAP kinase cascade, but also to activation of ERK (extracellular signal-regulated kinase) and p38. When expressed in fibroblasts, MLK2 co-localizes with active, dually phosphorylated JNK1/2 to punctate structures along microtubules. In an attempt to identify proteins that affect the activity and localization of MLK2, we have screened a yeast two-hybrid cDNA library. MLK2 and MLK3 interact with members of the KIF3 family of kinesin superfamily motor proteins and with KAP3A, the putative targeting component of KIF3 motor complexes, suggesting a potential link between stress activation and motor protein function.
Mesh Terms:
14-3-3 Proteins, 3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, COS Cells, Calcium-Binding Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Cycle Proteins, Cell Movement, Cytoskeletal Proteins, Enzyme Activation, GTP-Binding Proteins, Hippocalcin, JNK Mitogen-Activated Protein Kinases, Kinesin, MAP Kinase Kinase Kinases, Mice, Microinjections, Microtubules, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Nerve Tissue Proteins, Protein-Serine-Threonine Kinases, Proteins, Recombinant Proteins, Sequence Homology, Amino Acid, Substrate Specificity, Tyrosine 3-Monooxygenase, cdc42 GTP-Binding Protein, Saccharomyces cerevisiae, rac GTP-Binding Proteins
14-3-3 Proteins, 3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, COS Cells, Calcium-Binding Proteins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Cycle Proteins, Cell Movement, Cytoskeletal Proteins, Enzyme Activation, GTP-Binding Proteins, Hippocalcin, JNK Mitogen-Activated Protein Kinases, Kinesin, MAP Kinase Kinase Kinases, Mice, Microinjections, Microtubules, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Nerve Tissue Proteins, Protein-Serine-Threonine Kinases, Proteins, Recombinant Proteins, Sequence Homology, Amino Acid, Substrate Specificity, Tyrosine 3-Monooxygenase, cdc42 GTP-Binding Protein, Saccharomyces cerevisiae, rac GTP-Binding Proteins
EMBO J.
Date: Jan. 02, 1998
PubMed ID: 9427749
View in: Pubmed Google Scholar
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