【Abstract】 Objective To explore the effect of gain-of-function mutation SHP-2D61G/+ and SHP-2D61G/D61G on adhesion, migration and proliferation of mice MEFs cell, and to study the expression levels of p-ERK in gain-of-function mutation SHP-2 of MEFs cells. Methods The mice were mated to establish SHP-2D61G/+ 、SHP-2D61G/D61G gain-of-function mutation MEFs, and were immortalized by SV40T antigen. The effect of Gain-of-Function Mutation SHP-2 D61G/+ 、SHP-2D61G/D61G on the adhesion ability of MEFs cell was detected by cell adhesion assay. The transwell migration in vitro was applied to detect the effect of Gain-of-Function Mutation SHP-2 D61G/+ 、SHP-2D61G/D61G on migration ability of MEFs cell. The effect of gain-of-function mutation SHP-2 D61G/+ 、SHP-2D61G/ D61G on proliferation ability of MEFs cell was tested by MTT, and Western Blot was used to check the p-ERK expression. Results (1) Compared with control group, SHP-2D61G/+ 、SHP-2D61G/D61G gain-of-function mutation of MEFs cell significantly increased in the number of adherent cells, the difference had statistically significant. (2) Compared with control group, SHP-2D61G/+、SHP-2D61G/D61G gain-of-function mutation of MEFs cell significantly increased in the number of migration cells, there was significant difference. (3) The results of MTT showed that the proliferative capacity of the MEFs cell after SHP-2D61G/+ 、SHP-2D61G/D61G activating mutations were stronger than the control group, the difference had statistically significant. (4) Western Blot showed that compared with control group , whether just adherent or adherent after 30min and 60min, the p-ERK expression level of SHP-2D61G/+、SHP-2D61G/D61G were all increased. Conclusion The adhesion, migration and proliferation ability of mouse MEFs cell can be promoted by SHP-2 D61G/+ 、SHP-2D61G/D61G gain-of-function mutation. The level of p-ERK was increased in SHP-2 activating mutations MEFs cells.