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. 2022 May 11;10(5):1112. doi: 10.3390/biomedicines10051112

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Interaction between Src and Wnt signaling pathway. With Wnt stimulation, Src associates with LRP5/6 and ROR1/2 receptors and is activated. In addition, Src binding to Disheveled ensures Src activation and Src in turn phosphorylates Tyr18, 27, and 275 of Dishevelled, contributing to Wnt signaling. Furthermore, Src phosphorylates Fzd at Tyr552 to stimulate Wnt signaling. However, LRP5/6 Tyr1460 phosphorylation by Src leads to a negative regulation of Wnt signaling. In particular, Src phosphorylates β-catenin Tyr333, facilitating a nuclear translocation along with association with PKM2. Remarkably, p-Ser9 GSK-3β, which is induced by ROCK1, is able to phosphorylate Src at Ser493 and Ser51, leading to Src inactivation while phosphorylating in certain circumstances at Ser43, leading to its activation.