Abstract
Signaling molecules that bind to chemokine receptors should play key roles in regulation of cell migration induced by chemokines. To characterize the CCR1-mediated cellular signal transduction mechanism, we used the yeast two-hybrid system to identify a cellular ligand for CCR1. LZIP, which has been known as a transcription factor in various cell types, was identified as a CCR1 binding protein. Although the ability of LZIP to bind DNA is possibly what allows it to function as a transcription factor, its detailed function and participation in chemotaxis have not been established. We found that LZIP binds to CCR1 based on results of a mammalian two-hybrid assay and immunoprecipitation experiments. The 21-260 residues of LZIP were essential for interaction with CCR1. Results from a chemotaxis assay using LZIP transfected cells showed that LZIP enhanced Lkn-1-induced chemotaxis, whereas the chemotactic activities induced by other CC chemokines that bind to CCR1, including MIP-1alpha, RANTES, or HCC-4, were not affected by LZIP overexpression. These data indicate that LZIP binds to CCR1 and that the interaction between CCR1 and LZIP participates in regulation of Lkn-1-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1.
MeSH terms
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Animals
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Base Sequence
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Bone Neoplasms / metabolism
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Bone Neoplasms / pathology
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CHO Cells / drug effects
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CHO Cells / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cell Line / drug effects
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Cell Line / metabolism
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Cell Line, Tumor / metabolism
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5 / pharmacology
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Chemokines, CC / pharmacology*
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Chemokines, CC / physiology
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Chemotaxis / drug effects*
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Chemotaxis / physiology
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Cricetinae
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Cricetulus
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Cyclic AMP Response Element-Binding Protein
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Humans
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Kidney
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Leucine Zippers / genetics
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Leucine Zippers / physiology
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Macrophage Inflammatory Proteins / pharmacology
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Molecular Sequence Data
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Monocytes / drug effects
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Monocytes / metabolism
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Osteosarcoma / metabolism
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Osteosarcoma / pathology
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Protein Binding
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Protein Structure, Tertiary
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RNA, Small Interfering / pharmacology
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Receptors, CCR1
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Receptors, Chemokine / metabolism*
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Recombinant Fusion Proteins / physiology
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Sequence Deletion
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Signal Transduction / physiology
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Structure-Activity Relationship
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transfection
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Two-Hybrid System Techniques
Substances
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CCL16 protein, human
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CCR1 protein, human
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CREB3 protein, human
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Chemokine CCL3
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Chemokine CCL4
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Chemokine CCL5
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Chemokines, CC
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Cyclic AMP Response Element-Binding Protein
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Macrophage Inflammatory Proteins
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RNA, Small Interfering
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Receptors, CCR1
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Receptors, Chemokine
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Recombinant Fusion Proteins
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Transcription Factors