biostudies-literatureHoffman LMNCI NIH HHSNIGMS NIH HHSar100https://www.ebi.ac.uk/biostudies/studies/S-EPMC9582803biostudies-literatureUnknown33(11)The small heat shock protein HspB1, also known as Hsp25/27, is a ubiquitously expressed molecular chaperone that responds to mechanical cues. Uniaxial cyclic stretch activates the p38 mitogen-activated protein kinase (MAPK) signaling cascade and increases the phosphorylation of HspB1. Similar to the mechanosensitive cytoskeletal regulator zyxin, phospho-HspB1 is recruited to features of the stretch-stimulated actin cytoskeleton. To evaluate the role of HspB1 and its phosphoregulation in modulating cell function, we utilized CRISPR/Cas9-edited HspB1-null cells and determined they were altered in behaviors such as actin cytoskeletal remodeling, cell spreading, and cell motility. In our model system, expression of WT HspB1, but not nonphosphorylatable HspB1, rescued certain characteristics ofMolecular biology of the cellPhosphorylation of the small heat shock protein HspB1 regulates cytoskeletal recruitment and cell motility.PMC9582803P30 CA042014R01 GM050877Beckerle MCJensen CCHoffman LMfalsePhosphorylation of the small heat shock protein HspB1 regulates cytoskeletal recruitment and cell motility.The small heat shock protein HspB1, also known as Hsp25/27, is a ubiquitously expressed molecular chaperone that responds to mechanical cues. Uniaxial cyclic stretch activates the p38 mitogen-activated protein kinase (MAPK) signaling cascade and increases the phosphorylation of HspB1. Similar to the mechanosensitive cytoskeletal regulator zyxin, phospho-HspB1 is recruited to features of the stretch-stimulated actin cytoskeleton. To evaluate the role of HspB1 and its phosphoregulation in modulating cell function, we utilized CRISPR/Cas9-edited HspB1-null cells and determined they were altered in behaviors such as actin cytoskeletal remodeling, cell spreading, and cell motility. In our model system, expression of WT HspB1, but not nonphosphorylatable HspB1, rescued certain characteristics of2022-01-01T00:00:00Z2022 Sep2025-04-25T19:31:16.325Z2025-04-06T08:02:20.797ZS-EPMC95828033576732010.1091/mbc.E22-02-0057