SHP-1 protein expression is stabilized by the integrin α2β1 receptor. (A) Immunoblots of total cell lysates from C2C12 cells of the designated genotype, probed for either SHP-1 or SHP-2. Note the marked increase in SHP-1 expression in α2β1⁺ cells. Bar graphs represent mean ± SEM of the SHP-1 or SHP-2 expression normalized to tubulin (n ≥ 3); ***P < .001. (B) Effective knockdown of integrin α2 expression in HT-1080 cells (left) using a combination of 2 validated siRNAs targeting different regions of α2 mRNA. The expression of integrin α2 and SHP-1 resulting from each siRNA concentration treatment was analyzed by immunoblotting with GAPDH as a loading control. (Right) Knockdown of EphA2. Note that knockdown of integrin α2 drastically reduces the SHP-1 levels, whereas depletion of EphA2 has no effects. (C) Total SHP-1 levels in cell lysates from mouse pulmonary microvascular endothelial cells (ECs) or whole organ lysates as indicated from wild-type or α2β1^−/− mice. At the far right, liver from wild-type or α2β1^−/− mice probed for SHP-2. (D) Quantification of the SHP-1 expression in organs from 5 different wild-type or α2β1^−/− mice. Means ± SEMs; *P < .05. (E) Tyrosine phosphatase activity of immunoprecipitated SHP-1 from livers derived from wild-type or α2β1^−/− mice. The values in the bottom panel represent means ± SEMs (n = 3); *P < .05.