uPAR only needs to bind to vitronectin in the matrix to prompt cells to extend lamellipodia and filopodia.

The uPA receptor (uPAR) is a loner. Jutting from the plasma membrane, it has no apparent connection to the cell interior. But, as Madsen et al. demonstrate on page 927, uPAR induces cells to cling tightly to a surface. The behavior might recruit other receptors and explain how the seemingly isolated uPAR exerts its influence.

Stimulating uPAR galvanizes cells—they attach to a surface, flatten, move, and divide. Cancer cells exploit the receptor's power by cranking up its expression. But based on its structure, uPAR seems like a signaling dead end, and researchers had assumed that uPAR handed off its messages by binding to integrins.

Madsen et al. tested that idea by replacing every amino acid in the receptor one at a time with alanine. They found...

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