A novelpathwayfromphosphorylation oftyrosine residues 239/240ofShc,contributing to suppress apoptosis byIL-3

protein kinase (MAPK)activation towards c-fos geneexpression. We examined thepossible involvement ofShcintheantiapoptotic activity ofIL-3. Conditional overexpression oftheShcSH2domain, adominant-negative mutant ofShc, wasfound toinduce apoptosis ofIL-3-dependent BaIF3cells alongwitha reduction ofc-mycgene expression. Apoptosis wasrescued bytheexogenously introduced c-mycgene. Since weidentify novel tyrosine phosphorylation sites ofShc:Y239andY240,their role oncell survival wastested bymutational analysis. Ba/F3cells expressing mutantShcY317F,whichis unable tostimulate efficiently theRaspathway, still showedresistance to apoptosis. However,cells expressing ShcY239/240F, whichisabletostimulate theRaspathway, weresensitive toapoptosis. Inthese cells, induction ofthec-mycgenewasreduced. These findings suggest thatanewsignalling pathway forcell survival isgenerated fromY239/240 ofShctothe nuclei involving c-mycgeneexpression. Keywtords: apoptosis/IL-3/Myc/Shc