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PMID:11238452
Citation |
Verhey, KJ, Meyer, D, Deehan, R, Blenis, J, Schnapp, BJ, Rapoport, TA and Margolis, B (2001) Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J. Cell Biol. 152:959-70 |
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Abstract |
The cargo that the molecular motor kinesin moves along microtubules has been elusive. We searched for binding partners of the COOH terminus of kinesin light chain, which contains tetratricopeptide repeat (TPR) motifs. Three proteins were found, the c-jun NH(2)-terminal kinase (JNK)-interacting proteins (JIPs) JIP-1, JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway. Concentration of JIPs in nerve terminals requires kinesin, as evident from the analysis of JIP COOH-terminal mutants and dominant negative kinesin constructs. Coprecipitation experiments suggest that kinesin carries the JIP scaffolds preloaded with cytoplasmic (dual leucine zipper-bearing kinase) and transmembrane signaling molecules (the Reelin receptor, ApoER2). These results demonstrate a direct interaction between conventional kinesin and a cargo, indicate that motor proteins are linked to their membranous cargo via scaffolding proteins, and support a role for motor proteins in spatial regulation of signal transduction pathways. |
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Keywords |
Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Amino Acid Sequence; Animals; Binding Sites; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line; Kinesin/chemistry; Kinesin/genetics; Kinesin/metabolism; LDL-Receptor Related Proteins; MAP Kinase Kinase Kinases/metabolism; Mice; Models, Biological; Molecular Motor Proteins/chemistry; Molecular Motor Proteins/genetics; Molecular Motor Proteins/metabolism; Molecular Sequence Data; Mutation; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/metabolism; Precipitin Tests; Protein Binding; Rats; Receptors, Lipoprotein/metabolism; Sequence Alignment; Signal Transduction; Two-Hybrid System Techniques |
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