Multiple cytokines induce the tyrosine phosphorylation of Shc and its association with Grb2 in hemopoietic cells.
The identification and characterization of proteins that become tyrosine-phosphorylated in response to growth factor stimulation is critical to furthering our understanding of the signal transduction pathways involved in regulating cell proliferation and differentiation. In this report we demonstrate that interleukin-3, erythropoietin, and steel factor all induce the tyrosine phosphorylation of the SH2 containing protein, p52shc. These studies were carried out with various human and murine cell lines to document that this is a common event in hemopoietic cells. We also show that upon tyrosine phosphorylation, p52shc becomes associated with the adaptor protein, Grb2. The formation of this complex may directly link tyrosine phosphorylation events to Ras activation in hemopoietic progenitors and may be a critical step in stimulating these cells to transit through G1 into S phase.
Cutler
R L
RL
Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, Canada.
Liu
L
L
Damen
J E
JE
Krystal
G
G
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D004921:Erythropoietin / Q000494:pharmacology; D051380:GRB2 Adaptor Protein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019089:Stem Cell Factor; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D019089:Stem Cell Factor; D004921:Erythropoietin; D014443:Tyrosine; D066246:ErbB Receptors