Related Experiment Video
Updated: Jul 5, 2025
07:16
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
19.8K
The LKB1-TSSK1B axis controls YAP phosphorylation to regulate the Hippo-YAP pathway.
Cho-Long Kim1, Su-Bin Lim1, Sue-Hee Choi1
1Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, Suwon, 16499, South Korea.
Cell Death & Disease
|January 20, 2024
Summary
TSSK1B phosphorylates Yes-associated protein (YAP) through novel pathways, acting as a tumor suppressor by inhibiting cellular proliferation and oncogenic transformation. This discovery highlights new regulatory mechanisms in the Hippo-YAP pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Yes-associated protein (YAP) is a key transcriptional coactivator in the Hippo pathway, crucial for tumorigenesis.
- YAP activity is regulated by phosphorylation from core Hippo pathway kinases, controlling its localization and function.
- Alternative YAP phosphorylation pathways independent of the core Hippo components are increasingly recognized.
Purpose of the Study:
- To identify novel regulators of YAP phosphorylation and activity.
- To investigate the role of TSSK1B, a CAMK superfamily member, in YAP regulation.
- To elucidate the molecular mechanisms by which TSSK1B impacts cellular proliferation and oncogenic transformation.
Main Methods:
- Investigated the interaction and phosphorylation of YAP by TSSK1B.
- Utilized biochemical assays to analyze YAP-TEAD complex formation.
- Assessed the effects of TSSK1B on cellular proliferation and oncogenic transformation in relevant models.
Main Results:
- TSSK1B acts as a negative regulator of YAP, suppressing proliferation and oncogenic transformation.
- TSSK1B directly phosphorylates YAP at Ser94 via the LKB1-TSSK1B axis, inhibiting YAP-TEAD complex formation.
- TSSK1B also inhibits YAP via phosphorylation at Ser127 through the TSSK1B-LATS1/2 axis.
Conclusions:
- TSSK1B is a novel negative regulator of YAP, functioning through distinct phosphorylation events.
- These findings reveal a new layer of multilevel regulation within the Hippo-YAP pathway.
- TSSK1B-mediated YAP inhibition offers potential therapeutic strategies for YAP-driven cancers.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
01:20The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
02:33Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
01:25cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
01:07MAPK Signaling Cascades
5.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.5K
02:14GTPases and their Regulation
8.4K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.4K