Protein tyrosine phosphatase α (PTPα) can stimulate the activity of Src-family kinases. The activation process involves modification of an intramolecular interaction on Src, whereby the Src homology 2 (SH2) domain, which is bound to an inhibitory phosphotyrosine located at the COOH-terminus of Src, becomes bound instead to a phosphotyrosine moiety on PTPα. This exposes the Src inhibitory phosphotyrosine, allowing PTPα to dephosphorylate it, which leads to Src activation. Zheng and Shalloway have found that PTPα is activated during mitosis, before Src activation is observed. Inactive tyrosine phosphorylated PTPα is bound by the Grb2 adapter protein, at the site on PTPα required for SH2 domain displacement. The authors found that increased phosphorylation on serine residues in PTPα led to reduced association of Grb2 with PTPα during mitosis, which correlated with the activation of Src. Additionally, during mitosis in PTPα–/– cells, Src was not activated, indicating that PTPα has an important physiological role in regulating the activity of Src.