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Exquisite regulation is required for cells to properly enter and exit the phases of the cell cycle. The transmembrane receptor-like protein tyrosine phosphatase RPTPα, an important protein that participates in the transition of the cell cycle from G2 to mitosis activates the protein tyrosine kinase c-Src in vivo. Mustelin and Hunter discuss new findings that describe the highly regulated activation of RPTPα and c-Src that occurs just before entry into the mitotic phase. These findings also raise several questions that pertain to redistribution of RPTPα in the cell, and the role of phosphorylation and dimerization in regulating RPTPα activity.