Abstract
Various human cancers express elevated levels of the receptor tyrosine kinases Met or Ron and v6-containing isoforms of CD44. The activation of Met and Ron requires the presence of such CD44 v6-containing isoforms that act as coreceptors. Three amino acids within the v6 sequence were identified by mutational analysis to be essential for the coreceptor function: EWQ in the rat sequence and RWH in human. Peptides comprising these three amino acids (the smallest containing only five amino acids) efficiently act as competitors and block ligand-dependent activation of Met or Ron and subsequent cell migration.
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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Cell Movement / physiology*
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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HT29 Cells
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Humans
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Hyaluronan Receptors / genetics
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Hyaluronan Receptors / metabolism*
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Molecular Sequence Data
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-met
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Rats
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Receptor Protein-Tyrosine Kinases / metabolism
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Receptors, Growth Factor / antagonists & inhibitors*
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Receptors, Growth Factor / metabolism
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Structure-Activity Relationship
Substances
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CD44v6 antigen
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Glycoproteins
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Hyaluronan Receptors
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Peptide Fragments
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Proto-Oncogene Proteins
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Receptors, Growth Factor
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MET protein, human
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Proto-Oncogene Proteins c-met
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RON protein
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Receptor Protein-Tyrosine Kinases