Shc regulates epidermal growth factor-induced activation of the JNK signaling pathway.
Two adaptor molecules, Grb2 and Shc, have been implicated in the extracellular signal-regulated kinase (ERK) activation by receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR). Here we show that the EGF-mediated ERK activation is abolished by loss of Grb2, whereas this response is not affected by loss of Shc. Conversely, the EGF-mediated c-Jun N-terminal kinase (JNK) activation is dependent on Shc, but not Grb2. These findings strongly support distinct roles for Grb2 and Shc in controlling ERK and JNK activation after EGF stimulation.
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan.
A
A
Hashimoto
M
M
Kurosaki
N
N
Gotoh
M
M
Shibuya
T
T
Kurosaki
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000235:genetics; D051380:GRB2 Adaptor Protein; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000187:drug effects*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases