scholarly journals Cytoskeleton-Associated Protein 4, a Promising Biomarker for Tumor Diagnosis and Therapy

2021 ◽  
Vol 7 ◽  
Author(s):  
Shuang-Xi Li ◽  
Juan Li ◽  
Li-Wei Dong ◽  
Zhi-Yong Guo
Keyword(s):  
Signal Transduction ◽  
Cancer Diagnosis ◽  
Therapeutic Strategy ◽  
Research Evidence ◽  
Tumor Biology ◽  
Tumor Promotion ◽  
Signal Transduction Pathways ◽  
Regulation Functions ◽  
Gene Status

Cytoskeleton-associated protein 4 (CKAP4) is located in the rough endoplasmic reticulum (ER) and plays an important role in stabilizing the structure of ER. Meanwhile, CKAP4 is also found to act as an activated receptor at the cell surface. The multifunction of CKAP4 was gradually discovered with growing research evidence. In addition to the involvement in various physiological events including cell proliferation, cell migration, and stabilizing the structure of ER, CKAP4 has been implicated in tumorigenesis. However, the role of CKAP4 is still controversial in tumor biology, which may be related to different signal transduction pathways mediated by binding to different ligands in various microenvironments. Interestingly, CKAP4 has been recently recognized as a serological marker of several tumors and CKAP4 is expected to be a tumor therapeutic target. Therefore, deciphering the gene status, expression regulation, functions of CKAP4 in different diseases may shed new light on CKAP4-based cancer diagnosis and therapeutic strategy. This review discusses the publications that describe CKAP4 in various diseases, especially on tumor promotion and suppression, and provides a detailed discussion on the discrepancy.

scholarly journals Evidence for a positive role of PtdIns5P in T-cell signal transduction pathways

FEBS Letters ◽  
2010 ◽  
Vol 584 (11) ◽  
pp. 2455-2460 ◽  
Author(s):  
Geoffrey Guittard ◽  
Eva Mortier ◽  
Hélène Tronchère ◽  
Guylène Firaguay ◽  
Audrey Gérard ◽  
...  
Keyword(s):  
Signal Transduction ◽  
T Cell ◽  
Signal Transduction Pathways ◽  
Positive Role ◽  
Cell Signal ◽  
Cell Signal Transduction

Role of Tiam 1 in Rac-Mediated Signal Transduction Pathways

1996 ◽  
pp. 253-265 ◽  
Author(s):  
J. G. Collard ◽  
G. G. M. Habets ◽  
F. Michiels ◽  
J. Stam ◽  
R. A. van der Kammen ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways

Fluoride mobilizes intracellular calcium and promotes Ca2+ influx in rat proximal tubules

1991 ◽  
Vol 261 (2) ◽  
pp. F318-F327 ◽  
Author(s):  
J. H. Dominguez ◽  
J. G. Garcia ◽  
J. K. Rothrock ◽  
D. English ◽  
C. Mann
Keyword(s):  
Signal Transduction ◽  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
G Protein ◽  
Pertussis Toxin ◽  
Time Course ◽  
Proximal Tubules ◽  
Signal Transduction Pathways ◽  
Pi Hydrolysis

In the renal proximal tubule, external Ca2+ ([Ca2+]o) is required for parathyroid hormone to elevate cytosolic Ca2+ ([Ca2+]i). However, other hormones increase [Ca2+]i in the absence of [Ca2+]o. These differences may arise from a diversity of signal transduction pathways acting on external and internal Ca2+ pools. However, Ca2+ influx may be necessary to expedite and maintain the rise of [Ca2+]i for a period after the initial surge. In this study, F- was used to probe the roles of intracellular Ca2+ mobilization, Ca2+ influx, and phosphoinositide (PI) hydrolysis on the surge of [Ca2+]i in rat proximal tubules. In the presence of external Ca2+; 1-20 mM F- evoked incremental rises of [Ca2+]i in tubules loaded with aequorin. Whereas 10 mM F- increased [Ca2+]i in the absence of [Ca2+]o, the time constant for the [Ca2+]i surge was increased. These findings are consistent with a role of Ca2+ influx on the effect of F- on [Ca2+]i. Indeed, 10 mM F- also enhanced the uptake of 45Ca2+, and promoted Ca2+ influx in aequorin- and fura-2-loaded, Ca(2+)-deprived tubules. In tubules, F- also activated PI hydrolysis with a time course that paralleled Ca2+ mobilization. The effect of F- on [Ca2+]i was not altered when the 39-kDa pertussis toxin substrate was inactivated with the toxin. This G protein was most likely Gi, because prostaglandin E2, an activator of Gi in tubules, dissociated the pertussis toxin-sensitive protein. The results support the notion that activation of a signal-transduction complex, the F- substrate, causes Ca2+ influx, mobilizes internal Ca2+, and activates PI hydrolysis in rat proximal tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Oxidation Impacts the Intracellular Signaling Machinery in Hematological Disorders

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 353
Author(s):  
Elena Tibaldi ◽  
Enrica Federti ◽  
Alessandro Matte ◽  
Iana Iatcenko ◽  
Anand B. Wilson ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Conformational Changes ◽  
Intracellular Signaling ◽  
Signal Transduction Pathways ◽  
Functional Connection ◽  
Intracellular Signaling Pathway ◽  
Hematological Disorders ◽  
Dynamic Coordination ◽  
Transduction Mechanisms

The dynamic coordination between kinases and phosphatases is crucial for cell homeostasis, in response to different stresses. The functional connection between oxidation and the intracellular signaling machinery still remains to be investigated. In the last decade, several studies have highlighted the role of reactive oxygen species (ROS) as modulators directly targeting kinases, phosphatases, and downstream modulators, or indirectly acting on cysteine residues on kinases/phosphatases resulting in protein conformational changes with modulation of intracellular signaling pathway(s). Translational studies have revealed the important link between oxidation and signal transduction pathways in hematological disorders. The intricate nature of intracellular signal transduction mechanisms, based on the generation of complex networks of different types of signaling proteins, revealed the novel and important role of phosphatases together with kinases in disease mechanisms. Thus, therapeutic approaches to abnormal signal transduction pathways should consider either inhibition of overactivated/accumulated kinases or homeostatic signaling resetting through the activation of phosphatases. This review discusses the progress in the knowledge of the interplay between oxidation and cell signaling, involving phosphatase/kinase systems in models of globally distributed hematological disorders.

Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1214-1221 ◽  
Author(s):  
Thomas Powles ◽  
Robert te Poele ◽  
Jonathan Shamash ◽  
Tracy Chaplin ◽  
David Propper ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Cytotoxic Agents ◽  
Complex Signal ◽  
Signal Transduction Pathways ◽  
Potent Inducer ◽  
Leukemic Cell Lines

Abstract Δ9-Tetrahydrocannabinol (THC) is the active metabolite of cannabis. THC causes cell death in vitro through the activation of complex signal transduction pathways. However, the role that the cannabinoid 1 and 2 receptors (CB1-R and CB2-R) play in this process is less clear. We therefore investigated the role of the CB-Rs in mediating apoptosis in 3 leukemic cell lines and performed microarray and immunoblot analyses to establish further the mechanism of cell death. We developed a novel flow cytometric technique of measuring the expression of functional receptors and used combinations of selective CB1-R and CB2-R antagonists and agonists to determine their individual roles in this process. We have shown that THC is a potent inducer of apoptosis, even at 1 × IC50 (inhibitory concentration 50%) concentrations and as early as 6 hours after exposure to the drug. These effects were seen in leukemic cell lines (CEM, HEL-92, and HL60) as well as in peripheral blood mononuclear cells. Additionally, THC did not appear to act synergistically with cytotoxic agents such as cisplatin. One of the most intriguing findings was that THC-induced cell death was preceded by significant changes in the expression of genes involved in the mitogen-activated protein kinase (MAPK) signal transduction pathways. Both apoptosis and gene expression changes were altered independent of p53 and the CB-Rs.

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