title: Substrate rigidity and force define form through tyrosine phosphatase and kinase pathways.
abstract: Cell forces define cell morphology, alterations in which are caused by tyrosine kinase and phosphatase mutations, which implies a causal linkage. Recent studies have shown that phosphotyrosine signaling is involved in force sensing for cells on flat surfaces. Early force-dependent activation of Src family kinases by phosphatases or cytoskeleton stretch leads to the activation of downstream signaling. In addition, force generation by cells depends on a feedback mechanism between matrix rigidity or force generation and myosin contractility. Components of the force-sensing pathway are linked to the integrin-cytoskeleton complex at sites of force application and serve as scaffolds for signaling processes. Thus, early events in force detection are mechanically induced cytoskeletal changes that result in biochemical signals to mechanoresponsive pathways that then regulate cell form.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Grégory
authors.initials: G
authors.lastname: Giannone
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D040542:Mechanotransduction, Cellular; D008954:Models, Biological; D009127:Muscle Rigidity; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases