Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2.
We recently purified and cloned a 145-kDa protein that becomes tyrosine phosphorylated and associated with Shc in response to multiple cytokines. Based on its predicated amino acid sequence and its enzymatic activity, we have called this protein SHIP, for Src homology 2-containing inositol phosphatase. To gain further insight into the intracellular pathways that this putative signal transduction intermediate might regulate we have investigated whether SHIP binds to intracellular proteins other than Shc. The results presented herein demonstrate that following interleukin-3 stimulation, SHIP binds to the tyrosine phosphatase, SHP2 (also called Syp, PTP1D, SHPTP2, and PTP2C) and that Shc is not present in these SHIP-SHP2 complexes. Time course studies reveal that SHIP's association with SHP2 is transient and is maximal at 10 min of stimulation with interleukin-3. We further show that the association of SHIP with SHP2 occurs through the direct interaction of the SH2 domain of SHIP with a pYXN(I/V) sequence within SHP2.
Liu
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The Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada.
Damen
J E
JE
Ware
M D
MD
Krystal
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G
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D007377:Interleukin-3 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D018909:src Homology Domains
D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D010744:Phosphoric Monoester Hydrolases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases