Using Shp2 siRNAs, Dox-inducible shRNAs, Shp2 binding defective Gab1 mutant, and PTP-inactive Shp2 mutant, we have provided evidence that inhibition of Gab1-Shp2 interaction and Shp2 PTP activity suppress Erk1/2 activation in the HCC827 lung adenocarcinoma cells that harbor a mutant EGFR. The gene discussed is GAB1; the disease is lung adenocarcinoma.