Abstract:
:Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces. At the molecular level, shuttling requires a specific tyrosine in FHL2, as well as phosphorylation by active FA kinase (FAK). Thus, we suggest that FHL2 phosphorylation by FAK is a critical, mechanically dependent step in signaling from soft matrices to the nucleus to inhibit cell proliferation by increasing p21 expression.
journal_name
Proc Natl Acad Sci U S Aauthors
Nakazawa N,Sathe AR,Shivashankar GV,Sheetz MPdoi
10.1073/pnas.1608210113subject
Has Abstractpub_date
2016-11-01 00:00:00pages
E6813-E6822issue
44eissn
0027-8424issn
1091-6490pii
1608210113journal_volume
113pub_type
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