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Phosphatidylinositol 3-kinase associates, via its Src homology 2 domains,
with the activated erythropoietin receptor
JE Damen, AL Mui, L Puil, T Pawson and G Krystal
Terry Fox Laboratory, B.C. Cancer Research Centre, Vancouver, Canada.
The erythropoietin receptor (EpR) belongs to a family of hematopoietin
receptors whose members lack tyrosine kinase activity. Nonetheless, within
minutes of binding Ep, a number of cellular proteins become transiently
phosphorylated on tyrosine residues. One of these proteins, as we and
others have shown previously, is the EpR itself. To identify the remaining
protein substrates, we have examined the antiphosphotyrosine
immunoprecipitates of lysates from Ba/F3 cells expressing high levels of
cell surface EpRs. We now present data showing that, in response to Ep, the
85-Kd regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase)
becomes immunoprecipitable with antiphosphotyrosine antibodies. This
appears to be due, in large part, to the specific association of PI
3-kinase with the tyrosine- phosphorylated EpR, either directly or through
a 93- or 70-Kd tyrosine- phosphorylated intermediate. The activity of this
EpR associated PI 3- kinase, assessed in anti-EpR immunoprecipitates, is
maximal within 2 minutes of incubation with Ep and returns almost to
baseline levels by 10 minutes. In vitro studies suggest that the
interaction between PI 3- kinase and the activated EpR is mediated by the
N- and C-terminal SH2 domains of p85 and tyrosine-phosphorylated motifs on
the EpR.
Volume 81,
Issue 12,
pp. 3204-3210,
06/15/1993
Copyright © 1993 by The American Society of Hematology

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