FIGURE 7.

Mutation of the SH2 domains of SHP1 results in a partial loss of its inhibitory effects on NPM-ALK. Transfection of SHP1 in ALK⁺ALCL cell line Karpas 299 resulted in a dramatic down-regulation of phosphorylated NPM-ALK as well as the total ALK protein level. In contrast, the SHP1 mutant (mutation in both the N-SH2 and C-SH2 domains, SHP1^NC-SH2) resulted in a partial decrease in the level of tyrosine phosphorylation of NPM-ALK, as compared with SHP1. The densitometry values were determined after normalization to the β-actin band. Results shown are representative of three independent experiments.