| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 103 === Lamins (lamin A/C, B1, and B2) are intermediate filaments that form nuclear lamina underlying the nuclear membrane. In addition to providing nuclear mechanical support, nuclear lamina can tether chromatins, which is important for epigenetic regulation and gene transcription. Mutations in the lamin genes, which affect nuclear lamina assembly and finally result in cell death, are associated with a group of diseases collectively referred as laminopathies. The phosphorylation of lamins at serine residues is known to involve in the regulation of nuclear lamina assembly. However, the role of tyrosine phosphorylation of lamins in this regard has not been explored. In this study, we show that lamin A, but not lamins C, B1, and B2, is tyrosine phosphorylated, which is suppressed by the specific Src inhibitor dasatinib. The Tyr45 of lamin A, one of the residues whose mutation are already known to associate with laminopathies, was identified as the major phosphorylation site for Src. Src overexpression or knockout affects nuclear lamina assembly and nucleus morphology. Ectopic expression of the lamin A mutant with a mutation at Tyr45 induced abnormal nuclear lamina and nucleus morphology. Taken together, our results suggest that the phosphorylation of lamin A at Tyr45 by Src may be important for proper nuclear lamina assembly and nucleus morphology, therefore implicating a potential role of Src in laminopathies.
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