Stepwise receptor activation

The FGF receptor gets its multiple phosphorylations not randomly but in a strictly ordered sequence, say Cristina Furdul, Erin Lew, Joseph Schlessinger, and Karen Anderson (Yale University, New Haven, CT). The intermediate phosphorylation states—neither fully off nor fully on—may act as members of a carefully controlled activation and recruitment pathway.

The Yale group relied on rapid reaction techniques, including time-resolved mass spectrometry, to catch events that others have missed. They saw sequential phosphorylations at five sites, with an invariant order of phosphorylation. For example, every triphosphorylated receptor had the same 3 sites phosphorylated.

“The fact that it's so precise, without any redundancy, suggests it's significant,” says Schlessinger. The mechanism for ordering is not yet known, but one possibility is that phosphorylation at each site simply has different kinetics.

One consequence is a stepwise...