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A point mutation at tyrosine 809 in the human colony stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity association with phosphatidylinositol 3 kinase or induction of c fos and junb genes



A point mutation at tyrosine 809 in the human colony stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity association with phosphatidylinositol 3 kinase or induction of c fos and junb genes



Proceedings of the National Academy of Sciences of the United States of America 87(17): 6738-6742



Substitution of phenylalanine for tyrosine-809 in the human colony-stimulating factor 1 receptor (CSF-1R) inhibited its ability to transduce ligand-dependent mitogenic signals in mouse NIH 3T3 cells. When combined with an "activating" mutation at codon 301 that induces constitutive CSF-1R tyrosine kinase activity, the codon 809 mutation suppressed ligand-independent cell transformation. Comparative mapping of tryptic phosphopeptides from mutant and wild-type CSF-1R indicated that tyrosine-809 is a site of ligand-dependent receptor phosphorylation in vivo. The mutant receptor was active as a tyrosine kinase in vitro and in vivo, underwent CSF-1-dependent association with a phosphatidylinositol 3-kinase, and induced expression of the protooncogenes c-fos and junB, underscoring its ability to trigger some of the known cellular responses to CSF-1. The mutant receptor is likely to be impaired in its ability to interact with critical cellular effectors whose activity is required for mitogenesis.

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Accession: 006958851

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PMID: 2168557


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