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

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1990 Sep 1

PMID 2168557

Citations 41

Authors

M F Roussel

S A Shurtleff

J R Downing

C J Sherr

Affiliations

Soon will be listed here.

Abstract

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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