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. 2024 Apr 26;22:244. doi: 10.1186/s12964-024-01623-9

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 2 — Non-canonical Wnt signaling pathways. The non-canonical Wnt/PCP pathway is involved in cell polarity and microtubule reorganization. Binding of the Wnt ligand to the FZD receptor activates the Wnt/PCP pathway either by recruiting the LRP5/6 or tyrosine kinase Ror2 receptor. This activates the GTPase RAC1 which activates the c-Jun N-terminal kinase (JNK) which leads to activation of the JUN transcription factor for expression of genes involved in cell fate and polarity. The Wnt/Ca2⁺activates phospholipase C (PLC) following binding of the Wnt ligand on the FZD/LRP5/6 receptor complex. Activation of PLC leads to the activation of inositol triphosphate (PIP3), which increases calcium (Ca2⁺) in the endoplasmic reticulum. Increased Ca2⁺ leads to binding interaction with calcium-calmodulin kinase II (CaMKII) and activation of the nuclear factor of activated T cells (NFAT) transcription factor for its nuclear translocation and transcriptional activation of target genes that are involved in the pro-inflammatory response