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

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.17.6738· OSTI ID:5323845

Roussel, M F ^[1]; Shurtleff, S A; Downing, J R ^[2]; Sherr, C J ^[3]

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1. Univ. of Tennessee, Memphis (USA)
2. Saint Jude Children's Research Hospital, Memphis, TN (USA)
3. Univ. of Tennessee College of Medicine, Memphis (USA) Saint Jude Children's Research Hospital, Memphis, TN (USA)

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 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.

• OSTI ID: 5323845
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:17; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ONCOGENES
MOLECULAR BIOLOGY
PHOSPHOTRANSFERASES
GENE REGULATION
RECEPTORS
GENE MUTATIONS
CELL TRANSFORMATIONS
CODONS
FIBROBLASTS
MAN
METHIONINE
MICE
MITOGENS
PHENYLALANINE
PHOSPHOPROTEINS
PHOSPHORUS 32
SULFUR 35
TYROSINE
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
GENES
HYDROXY ACIDS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MEMBRANE PROTEINS
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
PRIMATES
PROTEINS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
SULFUR ISOTOPES
TRANSFERASES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques