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M. Leonard, P.S. Zelenka, A.S. Menko; Multiple Roles for Src Family Kinases in Lens Cell Differentiation Through N–cadherin Junctions . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2941.
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© ARVO (1962-2015); The Authors (2016-present)
Src family kinase (SFK) activity is necessary to maintain the undifferentiated, proliferative state of lens epithelial cells and is also required for lens fiber cell differentiation. We now have investigated which SFK members are involved in these two signaling events, focusing on their function in association with N–cadherin junctions.
Immunoprecipitation and Western Blotting of microdissected embryonic day 10 chick lenses enabled us to determine in vivo differentiation–specific changes in the expression of SFK members and the association with N–cadherin complexes at four distinct stages of lens cell differentiation.
Multiple SFK members were expressed in the embryonic lens, each with a distinctive differentiation–specific pattern of expression. This indicated that there were unique roles for the different Src family members during lens cell differentiation. c–Src and Lyn were expressed most highly in undifferentiated lens epithelial cells, where SFKs are likely involved in signaling proliferation. Fyn expression increased as lens cells initiated differentiation and high expression was maintained during the differentiation process, suggesting a role for Fyn in fiber cell differentiation. c–Yes expression peaked in nuclear fiber cells, indicating a possible role for this SFK in lens fiber cell maturation. We examined whether the signaling function of different SFK members during differentiation is related to their association with N–cadherin junctions. For these studies we have focused on c–Src and Fyn. N–cadherin immunoprecipitates of microdissected lens fractions immunoblotted with antibodies to c–Src show that this family member was most highly associated with N–cadherin in lens epithelial cells. Since c–Src negatively regulates cadherin junctions we suggest that this is the mechanism by which c–Src maintains the cells in a migratory and proliferative state. In contrast, Fyn, which has been associated with signaling cell differentiation, was most highly associated with N–cadherin in differentiating lens cells. Consistent with a distinct role for different SFKs in N–cadherin junctions at different stages of lens differentiation, the highest SFK activity in N–cadherin junctional complexes was coincident with high c–Src and Fyn junctional association.
Differential expression of SFK members supports the hypothesis that individual SFK members have distinct functions in lens cell differentiation. The data also support the hypothesis that SFK signaling function is linked to N–cadherin junctions.
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