Abstract
The endophilin family of proteins function in clathrin-mediated endocytosis. Here, we have identified and cloned the rat germinal center kinase-like kinase (rGLK), a member of the GCK (germinal center kinase) family of c-Jun N-terminal kinase (JNK) activating enzymes, as a novel endophilin I-binding partner. The interaction occurs both in vitro and in cells and is mediated by the Src homology 3 domain of endophilin I and a region of rGLK containing the endophilin consensus-binding sequence PPRPPPPR. Overlay analysis of rat brain extracts demonstrates that endophilin I is a major Src homology 3 domain-binding partner for rGLK. Overexpression of full-length endophilin I activates rGLK-mediated JNK activation, whereas N- and C-terminal fragments of endophilin I block JNK activation. Thus, endophilin I appears to have a novel function in JNK activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Brain / metabolism
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Consensus Sequence
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Enzyme Activation
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Gene Library
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Humans
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism*
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Rats
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Sequence Homology, Amino Acid
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src Homology Domains
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Recombinant Fusion Proteins
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SH3GL2 protein, human
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MAP4K5 protein, human
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Map4k3 protein, rat
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Protein Serine-Threonine Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases