Unlike many signaling molecules that remain true to one receptor, vascular endothelial growth factor (VEGF) is a two-timer. As Ball et al. show on page 489, VEGF also activates the receptor for the related platelet-derived growth factor (PDGF). VEGF is involved in everything from wound repair to cancer, and the study is the first to catch it being unfaithful.

By prodding vascular cells to travel and divide, VEGF sparks formation and growth of blood vessels. PDGF is similar structurally and functionally. But although the growth factors are evolutionarily related–and so are their receptors–nobody had previously shown any cross-reactions.

Ball et al. chanced on the discovery when they noticed that VEGF stimulated mesenchymal stem cells (MSCs) to migrate and proliferate. No surprise, except that MSCs lack VEGF receptors. The cells kept moving when dosed with antibodies that block the VEGF receptor. But they halted after treatment with antibodies against PDGF receptors. The researchers also found that VEGF promoted receptor phosphorylation, a sign of activation.

The researchers don't yet know whether PDGF can latch onto VEGF receptors. Another mystery is under what conditions stimulating the PDGF receptor with VEGF, rather than its normal ligand, is advantageous. The growth factors might convey slightly different messages. To find out, scientists could determine whether the receptor's responses to the two growth factors occur at the same speed and activate similar downstream pathways.