In studies of developmental signaling pathways stimulated by the Wnt proteins and their receptors, Xenopus Wnt-5A (Xwnt-5A) and a prospective Wnt receptor, rat Frizzled 2 (Rfz2), have been shown to stimulate inositol signaling and Ca2+ fluxes in zebrafish [1] [2] [3]. As protein kinase C (PKC) isoforms can respond to Ca2+ signals [4], we asked whether expression of different Wnt and Frizzled homologs modulates PKC. Expression of Rfz2 and Xwnt-5A resulted in translocation of PKC to the plasma membrane, whereas expression of rat Frizzled 1 (Rfz1), which activates a Wnt pathway using beta-catenin but not Ca2+ fluxes [5], did not. Rfz2 and Xwnt-5A were also able to stimulate PKC activity in an in vitro kinase assay. Agents that inhibit Rfz2-induced signaling through G-protein subunits blocked Rfz2-induced translocation of PKC. To determine if other Frizzled homologs differentially stimulate PKC, we tested mouse Frizzled (Mfz) homologs for their ability to induce PKC translocation relative to their ability to induce the expression of two target genes of beta-catenin, siamois and Xnr3. Mfz7 and Mfz8 stimulated siamois and Xnr3 expression but not PKC activation, whereas Mfz3, Mfz4 and Mfz6 reciprocally stimulated PKC activation but not expression of siamois or Xnr3. These results demonstrate that some but not all Wnt and Frizzled signals modulate PKC localization and stimulate PKC activity via a G-protein-dependent mechanism. In agreement with other studies [1] [2] [3]. [6] [7] these data support the existence of multiple Wnt and Frizzled signaling pathways in vertebrates.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/s0960-9822(99)80310-8 | DOI Listing |
Cell Commun Signal
January 2025
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although cochlear glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identifies a distinct subpopulation, Frizzled10 positive (FZD10+) cells, as an important type of GC responsible for neuronal differentiation in mouse cochlea.
View Article and Find Full Text PDFJ Cell Biochem
January 2025
Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
tRNA-derived fragments (tRFs) are a newly recognized class of small noncoding RNAs (sncRNAs) that play significant roles in various diseases. The Wnt pathway plays a key role in various physiological processes such as embryonic development, tissue renewal and regeneration. In the regulation of Wnt/β-catenin, Forkhead box k1(FOXK1), Frizzled class receptor 3 (FZD3), and Wnt5b can be targeted and inhibited by three tRFs: tRF3008A targets FOXK1 to inhibit colorectal cancer (CRC), 5'-tiRNAVal targets FZD3 to inhibit breast cancer (BrC), and tRF-22-8BWS7K092 targets Wnt5b to induce ferroptosis in lung cells.
View Article and Find Full Text PDFbioRxiv
January 2025
Department of Cell Biology, Van Andel Institute, Grand Rapids, Michigan, 49503, USA RRID: SCR_021956.
Hematopoietic stem and progenitor cells (HSPCs) arise only during embryonic development, and their identity specification, emergence from the floor of the dorsal aorta, and proliferation are all tightly regulated by molecular mechanisms such as signaling cues. Among these, Wnt signaling plays an important role in HSPC specification, differentiation, and self-renewal, requiring precise modulation for proper development and homeostasis. Wnt signaling is initiated when a Wnt ligand binds to cell surface receptors such as those encoded by the gene family, activating intracellular signaling pathways that regulate gene expression.
View Article and Find Full Text PDFStem Cell Reports
December 2024
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, University of Toronto, Toronto, ON, Canada. Electronic address:
During gastrulation, Wnt-β-catenin signaling dictates lineage bifurcation generating different mesoderm cell types. However, the specific role of Wnt receptors in mesoderm specification remains elusive. Using selective Frizzled (FZD) and LRP5/6 antibody-based agonists, we examined FZD receptors' function during directed mesoderm differentiation of human pluripotent stem cells (hPSCs).
View Article and Find Full Text PDFRegen Ther
March 2025
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
Background: Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!