Phosphorylation of GATA-6 is required for vascular smooth muscle cell differentiation after mTORC1 inhibition

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Science Signaling  12 May 2015:
Vol. 8, Issue 376, pp. ra44
DOI: 10.1126/scisignal.2005482

Blocking proliferation to keep blood vessels open

A treatment option for clearing blood vessels narrowed by atherosclerotic plaques is angioplasty and stenting, the insertion of a tube to help keep the blood vessel open. However, stents can trigger proliferation of the vascular smooth muscle cells resulting in renarrowing of the vessel. To avoid this complication, stents may contain the drug rapamycin, which is released to limit the proliferation and promote the differentiation of vascular smooth muscle cells. Xie et al. found that these effects of rapamycin on vascular smooth muscle cells required phosphorylation of the transcription factor GATA-6, which increased its stability and function. Various experiments indicated that Akt2 may be the kinase that phosphorylated GATA-6, and injured arteries in Akt2-null mice developed thicker blood vessel walls than those in control mice. Overexpression of a phosphorylation-mimetic form of GATA-6 prevented thickening of the blood vessel walls in Akt2-null mice after injury to a greater extent than did a phosphorylation-deficient mutant.

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