Exposure of cells to phorbol ester activates protein kinase C (PKC) to induce apoptosis or differentiation, depending on the cellular context. In erythroblastic cell lines, TF-1 and D2, upregulation of the RhoA signaling promotes phorbol ester-induced apoptosis through activating Rho-associated kinase (ROCK)/phosphorylation of myosin light chain (MLC), thus generating membrane contraction force. As a result, cell adhesion is inhibited and death receptor-mediated death pathway is activated in these cells with a concurrent changes in nucleocytoplasmic signaling for protein trafficking. A microtubule-regulated GEF-H1, which is a specific RhoA activator, was identified to contribute to RhoA activation in these cells. Thus, a cytoskeleton-regulated RhoA signaling cooperates with PKC activation constitutes a cellular context to determine the cell fate in response to phorbol ester stimulation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11373-005-9056-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Loss of Affects m6A Modification but Not Semen Characteristics in Bull Spermatozoa.
Int J Mol Sci
January 2025
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University, Hohhot 010070, China.
N6-methyladenosine (m6A) modification is a key methylation modification involved in reproductive processes. gene editing (MT) in cattle is known to enhance muscle mass and productivity. However, the changes in m6A modification in MT bull sperm remain poorly understood.
View Article and Find Full Text PDFProtocadherin-7 Regulates Monocyte Migration Through Regulation of Small GTPase RhoA and Rac1.
Int J Mol Sci
January 2025
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Protocadherin-7 (Pcdh7) is a member of the non-clustered protocadherin δ1 subgroup within the cadherin superfamily. Pcdh7 has been shown to control osteoclast differentiation via the protein phosphatase 2A (PP2A)-glycogen synthase kinase-3β (GSK3β)-small GTPase signaling axis. As protocadherins serve multiple biological functions, a deeper understanding of Pcdh7's biological features is valuable.
View Article and Find Full Text PDFThe Expression Regulation and Cancer-Promoting Roles of RACGAP1.
Biomolecules
December 2024
Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
RACGAP1 is a Rho-GTPase-activating protein originally discovered in male germ cells to inactivate Rac, RhoA and Cdc42 from the GTP-bound form to the GDP-bound form. GAP has traditionally been known as a tumor suppressor. However, studies increasingly suggest that overexpressed RACGAP1 activates Rac and RhoA in multiple cancers to mediate downstream oncogene overexpression by assisting in the nuclear translocation of signaling molecules and to promote cytokinesis by regulating the cytoskeleton or serving as a component of the central spindle.
View Article and Find Full Text PDFActivation of S1PR2 on macrophages and the hepatocyte S1PR2/RhoA/ROCK1/MLC2 pathway in vanishing bile duct syndrome.
PLoS One
January 2025
Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks.
View Article and Find Full Text PDFDedicator of Cytokinesis 2 regulates cytoskeletal actin dynamics and is essential for platelet biogenesis and functions.
Cardiovasc Res
January 2025
Department of Pharmacology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Aims: Dedicator of Cytokinesis 2 (DOCK2), a member of the DOCK family of Guanine nucleotide exchange factors that specifically act on the Rho GTPases including Rac and Cdc42, plays pivotal roles in the regulation of leukocyte homeostasis. However, its functions in platelets remain unknown.
Methods And Results: Using mice with genetic deficiency of DOCK2 (Dock2-/-), we showed that Dock2-/-mice exhibited a macrothrombocytopenic phenotype characterized as decreased platelet count and enlarged platelet size by transmission electron microscopy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!