PMID- 10340379
OWN - NLM
STAT- MEDLINE
DCOM- 19990608
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 20
DP  - 1999 May 20
TI  - Cell specific transformation by c-fms activating loop mutations is attributable
      to constitutive receptor degradation.
PG  - 3076-84
AB  - Expression of a receptor for human macrophage-colony stimulating factor (M-CSF or
      CSF-1), containing a point mutation which changes an aspartate to a valine at
      position 802 of the activating loop of the kinase domain, potently transforms the
      haemopoietic cell line FDC-P1 yet prevents Rat-2 fibroblast transformation. In
      order to understand this apparent paradox, aspartate 802 was changed by cassette 
      mutagenesis to each of the other 19 amino acids. All hydrophobic amino acid
      substitutions were transforming when tested in FDC-P1 cells yet inactivating when
      tested in Rat-2 fibroblasts. These same amino acid substitutions also activated
      receptor degradation, strongly suggesting a causal relationship between receptor 
      degradation and inactivation in fibroblasts. Point mutations or small deletions
      of Y708 within the kinase insert region of the mutant D802V receptor partly
      inhibited receptor degradation. The more stable D802V receptor derivatives were
      able to transform both FDC-P1 cells and Rat-2 fibroblasts, so establishing that
      the cell specific effect of the c-fmsD802V activating loop mutation is
      attributable to receptor degradation which accompanies kinase activation and
      prevents the transformation of Rat-2 but not of FDC-P1 cells.
FAU - Morley, G M
AU  - Morley GM
AD  - Cell Signalling Unit, Division of Paediatrics, Obstetrics and Gynaecology,
      Imperial College School of Medicine, Hammersmith Hospital, London, UK.
FAU - Uden, M
AU  - Uden M
FAU - Gullick, W J
AU  - Gullick WJ
FAU - Dibb, N J
AU  - Dibb NJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA Primers)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Transformation, Neoplastic/*genetics
MH  - DNA Primers
MH  - Humans
MH  - Hydrolysis
MH  - Mutagenesis, Insertional
MH  - Phenotype
MH  - Rats
MH  - Receptor, Macrophage Colony-Stimulating Factor/*genetics/*metabolism
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - 10.1038/sj.onc.1202646 [doi]
PST - ppublish
SO  - Oncogene. 1999 May 20;18(20):3076-84. doi: 10.1038/sj.onc.1202646.