title: The effect of differentiation induction on FAK and Src activity in live HMSCs visualized by FRET.
abstract: FAK and Src signaling play important roles in cell differentiation, survival and migration. However, it remains unclear how FAK and Src activities are regulated at the initial stage of stem cell differentiation. We utilized fluorescence resonance energy transfer (FRET)-based FAK and Src biosensors to visualize these kinase activities at the plasma membrane of human mesenchymal stem cells (HMSCs) under the stimulation of osteogenic, myoblastic, or neural induction reagents. Our results indicate that the membrane FAK and Src activities are distinctively regulated by these differentiation induction reagents. FAK and Src activities were both up-regulated with positive feedback upon osteogenic induction, while myoblastic induction only activated Src, but not FAK. Neural induction, however, transiently activated FAK and subsequently Src, which triggered a negative feedback to partially inhibit FAK activity. These results unravel distinct regulation mechanisms of FAK and Src activities during HMSC fate decision, which should advance our understanding of stem cell differentiation in tissue engineering.
authors.affiliation: Biomaterials and Live Cell Imaging Institute, Chongqing University of Science and technology, Chongqing, People's Republic of China ; Beckman Institute for Advanced Science and Technology, Center for Biophysics and Computational Biology, Department of Integrative and Molecular Physiology, Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, Illinois, United States of America.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liao
authors.forename: Shaoying
authors.initials: S
authors.lastname: Lu
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Wu
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhuo
authors.forename: Qin
authors.initials: Q
authors.lastname: Peng
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D002454:Cell Differentiation; D002478:Cells, Cultured; D004789:Enzyme Activation; D025461:Feedback, Physiological; D031541:Fluorescence Resonance Energy Transfer; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D023822:Tissue Engineering; D018631:ras Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000081247:CSK Tyrosine-Protein Kinase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; C000631346:CSK protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins