(A) Effect of CRKL suppression on relative proliferation of NSCLC cell lines and AALE cells. Top, Immunoblot of CRKL proteins in each cell line expressing control shRNAs or two distinct CRKL-specific shRNAs. Bottom, Cell proliferation 6 d after infection with indicated shRNAs for each cell line. Data represent mean + s.d of six replicate measurements.
(B) Effect of expression of shRNA-resistant CRKL on the proliferation of H1755 cells expressing CRKL-specific shRNAs. Top, Generation of a shRNA-resistant CRKL cDNA (CRKLsilent mutant). The 21-mer sequence targeted by shCRKL#1 is marked in red color. Middle, Immunoblot of CRKL 4 d after infection with indicated shRNAs in H1755 cells expressing a control vector or V5-epitope tagged CRKLsilent mutant. Bottom, Effect of CRKL suppression by CRKL-targeting shRNAs on the proliferation of H1755 cells expressing a control vector or CRKLsilent mutant. The shCRKL#2 and shCRKL#3 target the 3′UTR of endogenous CRKL mRNA.
(C) Effect of CRKL suppression on cleavage of PARP and Caspase-3 proteins in NSCLC cells. Immunoblots of PARP and Caspase-3 proteins in H1755 and HCC1833 cells expressing the indicated shRNAs.
(D) Effects of mutations on CRKL function in H1755 cells. Left, Schematic of CRKL mutants. Right, Effect of expressing wild-type or mutant CRKL on the proliferation of the H1755 cells expressing a CRKL-specific shRNA (shCRKL#3). Data represent mean + s.d. of six replicate measurements. * indicates p<0.0001 as compared to cells expressing a control vector and shCRKL#3.