title: Mechanosensing Controlled Directly by Tyrosine Kinases.
abstract: To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of contractile units causes transformation. We report here that knocking down the receptor tyrosine kinases (RTKs), AXL, and ROR2, alters rigidity sensing and increases the magnitude or duration of local contraction events, respectively. Phospho-AXL and ROR2 localize to contraction units and bind major contractile components, tropomyosin 2.1 (AXL), myosin IIA (AXL), and filamin A (ROR2). At a molecular level, phosphorylated AXL localizes to active myosin filaments and phosphorylates tropomyosin at a tyrosine critical for adhesion formation. ROR2 binding of ligand is unnecessary, but binding filamin A helps function. Thus, AXL and ROR2 alter rigidity sensing and consequently morphogenic processes by directly controlling local mechanosensory contractions without ligands.
authors: Mechanobiology Institute, National University of Singapore , Singapore 117411.
authors: Bo
authors: B
authors: Yang
authors: Mechanobiology Institute, National University of Singapore , Singapore 117411.
authors: Zi Zhao
authors: ZZ
authors: Lieu
authors: Department of Biological Sciences, Columbia University , New York, New York 10027, United States.
authors: Haguy
authors: H
authors: Wolfenson
authors: Mechanobiology Institute, National University of Singapore , Singapore 117411.
authors: Feroz M
authors: FM
authors: Hameed
authors: Mechanobiology Institute, National University of Singapore , Singapore 117411.|Department of Molecular Cell Biology, Weizmann Institute of Science , Rehovot 76100, Israel.
authors: Alexander D
authors: AD
authors: Bershadsky
authors: Mechanobiology Institute, National University of Singapore , Singapore 117411.|Department of Biological Sciences, Columbia University , New York, New York 10027, United States.
authors: Michael P
authors: MP
authors: Sheetz
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology*; D055785:Gene Knockdown Techniques; D006801:Humans; D040542:Mechanotransduction, Cellular; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000502:physiology*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C078717:ROR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: AXL; ROR2; Rigidity sensing; mechanotransduction; nano pillars; protein tyrosine kinases