Research ArticleCell Biology

MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity

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Science Signaling  31 Oct 2017:
Vol. 10, Issue 503, eaan3286
DOI: 10.1126/scisignal.aan3286

MARKing the switch from microtubules to actin

To enable them to carry out specialized functions, many cell types become polarized through the activity of various proteins, including the kinases of the MARK family. Sandí et al. found that MARK3 phosphorylated Ser151 in the cytoskeleton-associated protein ARHGEF2. This phosphorylation event caused ARHGEF2 to dissociate from microtubules and activate RHOA, resulting in the formation of focal adhesions and stress fibers and enabling the formation of three-dimensional structures by cultured cells. These effects were reversed by the PP2A-mediated dephosphorylation of Ser151 in ARHGEF2. Thus, the phosphorylation state of Ser151 of ARHGEF2 determines whether it is sequestered by the tubulin cytoskeleton or released to remodel the actin cytoskeleton and regulate cell polarity.