PMID- 7525552
OWN - NLM
STAT- MEDLINE
DCOM- 19941129
LR  - 20210212
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 44
DP  - 1994 Nov 4
TI  - c phosphorylation and activation of the IGF-I receptor in src-transformed cells.
PG  - 27315-21
AB  - Using a panel of src mutants partially defective for malignant transformation, 
      our laboratory has previously identified the insulin-like growth factor (IGF-I) 
      receptor as a protein whose tyrosine phosphorylation correlates with 
      transformation by src in embryonic chick cells (Kozma et al., 1990; Kozma and 
      Weber, 1990). It has not been clear, however, whether src-induced phosphorylation 
      altered the enzymatic or signaling properties of the IGF-I receptor and thus 
      whether the IGF-I receptor could be a functionally significant target for 
      pp60v-src. To examine the effect of src expression on the activity of the IGF-I 
      receptor, the human IGF-I receptor was expressed in Rat-1 fibroblasts 
      co-expressing the temperature-sensitive v-src mutant, tsLA29. The IGF-I receptor 
      exhibited an elevated level of tyrosine phosphorylation in src transformed cells 
      even in the absence of IGF-I treatment. Increased receptor phosphorylation 
      occurred rapidly when cells expressing a temperature-conditional src mutant were 
      shifted from the restrictive to the permissive temperature. Src-induced 
      phosphorylation of the receptor was correlated with an increase in the in vitro 
      tyrosine kinase activity of the receptor, both toward itself and exogenous 
      substrates. The src-induced increase in receptor activity was shown to be 
      dependent on tyrosine phosphorylation, as treatment with a tyrosine-specific 
      phosphatase lowered receptor activity. A kinase-defective mutant of the IGF-I 
      receptor also became constitutively phosphorylated in src-transformed cells, 
      ruling out a possible autocrine mechanism for this phosphorylation. Collectively 
      these data indicate that pp60v-src induces ligand-independent phosphorylation and 
      activation of the IGF-I receptor by an intracellular mechanism, consistent with 
      the possibility that receptor phosphorylation could contribute to the genesis of 
      the transformed phenotype.
FAU - Peterson, J E
AU  - Peterson JE
AD  - Department of Microbiology, University of Virginia, Charlottesville 22908.
FAU - Jelinek, T
AU  - Jelinek T
FAU - Kaleko, M
AU  - Kaleko M
FAU - Siddle, K
AU  - Siddle K
FAU - Weber, M J
AU  - Weber MJ
LA  - eng
GR  - CA 39076/CA/NCI NIH HHS/United States
GR  - CA 40042/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.2 (Oncogene Protein pp60(v-src))
SB  - IM
GS  - src
MH  - Animals
MH  - Cell Line
MH  - *Cell Transformation, Viral
MH  - *Genes, src
MH  - Humans
MH  - Oncogene Protein pp60(v-src)/*metabolism
MH  - Phosphorylation
MH  - Phosphotyrosine
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptor, IGF Type 1/*metabolism
MH  - Time Factors
MH  - Transfection
MH  - Tyrosine/analogs & derivatives/metabolism
EDAT- 1994/11/04 00:00
MHDA- 1994/11/04 00:01
CRDT- 1994/11/04 00:00
PHST- 1994/11/04 00:00 [pubmed]
PHST- 1994/11/04 00:01 [medline]
PHST- 1994/11/04 00:00 [entrez]
AID - S0021-9258(18)46987-6 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Nov 4;269(44):27315-21.