The uncoupling of Shc activation from distal intracellular signalling in a cell line which expresses a truncated human epidermal growth factor receptor.
We have examined epidermal growth factor (EGF) signalling in a CHO cell line (CHO11) which expresses a human EGF receptor truncated at amino acid 990. Previous studies showed that EGF treatment of these cells failed to increase prostaglandin production or phospholipase A2 activity. In the current study EGF increased the tyrosine phosphorylation of the intracellular signalling protein Shc in CHO11 cells but did not activate either of the downstream signalling enzymes raf or mitogen activated protein kinase (MAPK). The uncoupling of Shc activation from distal signalling in CHO11 cells contrasts with other cells which express similar mutant EGF receptors. The failure of She to activate distal signalling may reflect qualitative differences in the way that this protein is activated or could result from the activation of an inhibitory signalling pathway.
McNeil
A
A
Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Larkins
R
R
Clark
S
S
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013329:Structure-Activity Relationship
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D004676:Myelin Basic Protein; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D011494:Protein Kinases; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf