scholarly journals Expressions of Sphingosine-1-phosphate (S1P) Receptors, Sphingosine Kinases in Malignant Bone and Soft Tissue Tumors, and The role of Sphingosine Kinase-1 in Growth of MFH Cell Lines

2011 ◽  
Vol 02 (02) ◽  
pp. 288-294
Author(s):  
Shin-ichiro Kishimoto ◽  
Toshihiro Akisue ◽  
Kenta Kishimoto ◽  
Hitomi Hara ◽  
Masaya Imabori ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Cell Lines ◽  
Sphingosine Kinase ◽  
Soft Tissue Tumors ◽  
Sphingosine Kinase 1 ◽  
S1p Receptors ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases

scholarly journals Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720

2004 ◽  
Vol 279 (50) ◽  
pp. 52487-52492 ◽  
Author(s):  
Maria L. Allende ◽  
Teiji Sasaki ◽  
Hiromichi Kawai ◽  
Ana Olivera ◽  
Yide Mi ◽  
...  
Keyword(s):  
Vascular Development ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Cellular Functions ◽  
Lymphocyte Trafficking ◽  
Signaling Molecule ◽  
Physiological Functions ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Receptor

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1.Sphk1null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in mostSphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from theSphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs ofSphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in theSphk1null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with theseSphk1null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

Sphingosine 1-phosphate signalling in cancer

2012 ◽  
Vol 40 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Nigel J. Pyne ◽  
Francesca Tonelli ◽  
Keng Gat Lim ◽  
Jaclyn S. Long ◽  
Joanne Edwards ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Sphingosine Kinase ◽  
Receptor Expression ◽  
Sphingosine Kinase 1 ◽  
Histone Deacetylase 1 ◽  
S1p Receptors ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

There is an increasing body of evidence demonstrating a critical role for the bioactive lipid S1P (sphingosine 1-phosphate) in cancer. S1P is synthesized and metabolized by a number of enzymes, including sphingosine kinase, S1P lyase and S1P phosphatases. S1P binds to cell-surface G-protein-coupled receptors (S1P1–S1P5) to elicit cell responses and can also regulate, by direct binding, a number of intracellular targets such as HDAC (histone deacetylase) 1/2 to induce epigenetic regulation. S1P is involved in cancer progression including cell transformation/oncogenesis, cell survival/apoptosis, cell migration/metastasis and tumour microenvironment neovascularization. In the present paper, we describe our research findings regarding the correlation of sphingosine kinase 1 and S1P receptor expression in tumours with clinical outcome and we define some of the molecular mechanisms underlying the involvement of sphingosine kinase 1 and S1P receptors in the formation of a cancer cell migratory phenotype. The role of sphingosine kinase 1 in the acquisition of chemotherapeutic resistance and the interaction of S1P receptors with oncogenes such as HER2 is also reviewed. We also discuss novel aspects of the use of small-molecule inhibitors of sphingosine kinase 1 in terms of allosterism, ubiquitin–proteasomal degradation of sphingosine kinase 1 and anticancer activity. Finally, we describe how S1P receptor-modulating agents abrogate S1P receptor–receptor tyrosine kinase interactions, with potential to inhibit growth-factor-dependent cancer progression.

scholarly journals Role of sphingosine kinase 1 and sphingosine‐1‐phosphate in CD40 signaling and IgE class switching

2014 ◽  
Vol 28 (10) ◽  
pp. 4347-4358 ◽  
Author(s):  
Eugene Y. Kim ◽  
Jamie L. Sturgill ◽  
Nitai C. Hait ◽  
Dorit Avni ◽  
Evelyn C. Valencia ◽  
...  
Keyword(s):  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Class Switching ◽  
Sphingosine 1 Phosphate

scholarly journals Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Ling-Wei Hii ◽  
Felicia Fei-Lei Chung ◽  
Chun-Wai Mai ◽  
Pei Yuen Ng ◽  
Chee-Onn Leong
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Signaling Axis ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
Research Findings

Sphingosine kinases (SPHKs) are conserved lipid enzymes that catalyze the formation of sphingosine-1-phosphate (S1P) through ATP-dependent phosphorylation of sphingosine. Two distinct SPHK isoforms, namely SPHK1 and SPHK2, have been identified to date, and the former has been implicated for its oncogenic roles in cancer development and progression. While SPHK1 signaling axis has been extensively studied in non-stem breast cancer cells, recent evidence has emerged to suggest a role of SPHK1 in regulating cancer stem cells (CSCs). With the clinical implications of CSCs in disease relapse and metastasis, it is believed that therapeutic approaches that can eradicate both non-stem cancer cells and CSCs could be a key to cancer cure. In this review, we first explore the oncogenic functions of sphingosine kinase 1 in human cancers and summarize current research findings of SPHK1 signaling with a focus on breast cancer. We also discuss the therapeutic potentials and perspectives of targeting SPHK1 signaling in breast cancer and cancer stem cells. We aim to offer new insights and inspire future studies looking further into the regulatory functions of SPHK1 in CSC-driven tumorigenesis, uncovering novel therapeutic avenues of using SPHK1-targeted therapy in the treatment of CSC-enriched refractory cancers.

scholarly journals The Functional Role of Sphingosine Kinase 2

2021 ◽  
Vol 8 ◽  
Author(s):  
Rocio Diaz Escarcega ◽  
Louise D. McCullough ◽  
Andrey S. Tsvetkov
Keyword(s):  
Sphingosine Kinase ◽  
Telomere Maintenance ◽  
Sphingosine Kinase 1 ◽  
Lipid Molecule ◽  
Nuclear Signaling ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
Associated Conditions ◽  
Health And Disease

Sphingosine-1-phosphate (S1P) is a bioactive lipid molecule that is present in all eukaryotic cells and plays key roles in various extracellular, cytosolic, and nuclear signaling pathways. Two sphingosine kinase isoforms, sphingosine kinase 1 (SPHK1) and sphingosine kinase 2 (SPHK2), synthesize S1P by phosphorylating sphingosine. While SPHK1 is a cytoplasmic kinase, SPHK2 is localized to the nucleus, endoplasmic reticulum, and mitochondria. The SPHK2/S1P pathway regulates transcription, telomere maintenance, mitochondrial respiration, among many other processes. SPHK2 is under investigation as a target for treating many age-associated conditions, such as cancer, stroke, and neurodegeneration. In this review, we will focus on the role of SPHK2 in health and disease.

scholarly journals Localization of Sphingosine Kinase-1 in Mouse Sperm Acrosomes

2005 ◽  
Vol 53 (2) ◽  
pp. 243-247 ◽  
Author(s):  
Kenji Matsumoto ◽  
Yoshiko Banno ◽  
Takashi Murate ◽  
Yukihiro Akao ◽  
Yoshinori Nozawa
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Sphingosine Kinase ◽  
Lipid Mediator ◽  
Sphingosine Kinase 1 ◽  
Rt Pcr ◽  
Mouse Sperm ◽  
S1p Receptors ◽  
Acrosomal Reaction ◽  
Sphingosine 1 Phosphate

Sphingosine kinase (SPHK) catalyzes sphingosine phosphorylation to form a bioactive lipid mediator, sphingosine-1-phosphate (S1P). In the current study, we report the presence of SPHK-1 in mouse spermatozoa. SPHK-1 was localized to the acrosomes of spermatozoa, and its expression was proven by RT-PCR and Western blot analysis. SPHK activity of mouse spermatozoa was 18.1 pmol/min/mg protein. Furthermore, we identified the presence of the S1P receptors S1P1, S1P2, S1P3, and S1P5, in mouse spermatozoa by RT-PCR. These results suggest that S1P produced by SPHK-1 would play a role in the acrosomal reaction through S1P receptors.

scholarly journals Characterizing Sphingosine Kinases and Sphingosine 1-Phosphate Receptors in the Mammalian Eye and Retina

2018 ◽  
Vol 19 (12) ◽  
pp. 3885 ◽  
Author(s):  
Hunter Porter ◽  
Hui Qi ◽  
Nicole Prabhu ◽  
Richard Grambergs ◽  
Joel McRae ◽  
...  
Keyword(s):  
Stress Responses ◽  
Expression Profiles ◽  
Receptor Gene ◽  
Light Stress ◽  
Rat Tissues ◽  
Light Damage ◽  
S1p Receptors ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases

Sphingosine 1-phosphate (S1P) signaling regulates numerous biological processes including neurogenesis, inflammation and neovascularization. However, little is known about the role of S1P signaling in the eye. In this study, we characterize two sphingosine kinases (SPHK1 and SPHK2), which phosphorylate sphingosine to S1P, and three S1P receptors (S1PR1, S1PR2 and S1PR3) in mouse and rat eyes. We evaluated sphingosine kinase and S1P receptor gene expression at the mRNA level in various rat tissues and rat retinas exposed to light-damage, whole mouse eyes, specific eye structures, and in developing retinas. Furthermore, we determined the localization of sphingosine kinases and S1P receptors in whole rat eyes by immunohistochemistry. Our results unveiled unique expression profiles for both sphingosine kinases and each receptor in ocular tissues. Furthermore, these kinases and S1P receptors are expressed in mammalian retinal cells and the expression of SPHK1, S1PR2 and S1PR3 increased immediately after light damage, which suggests a function in apoptosis and/or light stress responses in the eye. These findings have numerous implications for understanding the role of S1P signaling in the mechanisms of ocular diseases such as retinal inflammatory and degenerative diseases, neovascular eye diseases, glaucoma and corneal diseases.

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