STAT5A stays out of the nucleus (blue) when Rac1 is removed (bottom).

Rac proteins are most familiar in the context of cytoskeletal regulation. Now, Kawashima et al. (page 937) find that Rac1 and its regulator help STAT transcriptional activators to get into the nucleus.

STAT proteins signal downstream of cytokine receptors. These researchers previously reported an association between STAT3 and the GTPase-activating protein MgcRacGAP. Here they report that Rac1 and MgcRacGAP bind STAT5A, and that the association between MgcRacGAP and STAT5A is enhanced by IL-3 signaling. Both Rac1 and MgcRacGAP were necessary for efficient entry of STAT5A into the nucleus, and in semipermeabilized cells a dominant-negative Rac1 prevented binding of STAT5A to importin-α, and thus nuclear entry.

Others have previously shown, using armadillo proteins as import substrates, that Rac1 has a nuclear localization sequence (NLS) that is active when Rac1 is in its active,...

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