Abstract
The intracellular domain (ICD) of the low-density lipoprotein receptor-related protein (LRP) functionally interacts with adaptor proteins both as an integral part of the receptor polypeptide and after proteolytic release. Identification of such adaptors has been difficult because the ICD is self-activating in conventional transcription factor-based yeast two-hybrid screens. We adopted an alternative screen for the ICD that depends on the activation of the Ras-signaling pathway and uncovered the transcription factor MafB as novel ICD interacting protein. MafB is a regulator of hindbrain segmentation and interacts with the ICD through a leucine zipper domain. The ICD co-localizes with MafB to the nucleus and negatively regulates its transcriptional activity, suggesting a possible role for LRP in brain development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Avian Proteins*
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Brain / embryology*
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Brain / metabolism
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Cell Line
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Cell Nucleus / metabolism
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DNA, Complementary / metabolism
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DNA-Binding Proteins*
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Genes, Reporter
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Glutathione Transferase / metabolism
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Humans
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Immunohistochemistry
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Ligands
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Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
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MafB Transcription Factor
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Mice
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Mice, Knockout
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Microscopy, Fluorescence
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Models, Genetic
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Molecular Sequence Data
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Oncogene Proteins / physiology
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Protein Binding
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Protein Structure, Tertiary
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Surface Plasmon Resonance
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Time Factors
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Trans-Activators / physiology
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Transcription Factors*
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Transcription, Genetic
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Transfection
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Two-Hybrid System Techniques
Substances
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Avian Proteins
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DNA, Complementary
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DNA-Binding Proteins
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Ligands
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Low Density Lipoprotein Receptor-Related Protein-1
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MAFB protein, human
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MafB Transcription Factor
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Mafb protein, mouse
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Oncogene Proteins
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Trans-Activators
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Transcription Factors
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Glutathione Transferase