Rewiring of sIgM-Mediated Intracellular Signaling through the CD180 Toll-like Receptor

Porakishvili, Nino; Vispute, Ketki; Steele, Andrew J.; Rajakaruna, Nadeeka; Kulikova, Nina; Tsertsvadze, Tamar; Nathwani, Amit C.; Damle, Rajendra N.; Clark, Edward A.; Kanti, R.; Chiorazzi, Nicholas; Lydyard, Peter M.

doi:10.2119/molmed.2014.00265

Cited by 12 publications

(25 citation statements)

References 66 publications

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“…The levels of cell surface CD180 are higher in CLL cases with mutated IGHV , making CD180, like CD150, a potential surrogate prognostic marker of CLL outcome [ 21 ]. CD180 ligation can modulate BCR signaling in CLL B cells, preventing pro-survival signals and inducing apoptosis [ 37 ]. We found that CD150 cell surface expression positively correlated with CD180 expression on CLL B cells.…”

Section: Discussionmentioning

confidence: 99%

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

et al. 2017

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Cell surface expression of CD150 and CD180 receptors in chronic lymphocytic leukemia (CLL) associates with mutational IGHV status and favourable prognosis. Here we show a direct correlation between cell surface expression and colocalization of these receptors on CLL B cells. In the absence of CD150 and CD180 on the cell surface both receptors were expressed in the cytoplasm. The CD150 receptor was colocalized with markers of the endoplasmic reticulum, the Golgi apparatus and early endosomes. In contrast, CD180 was detected preferentially in early endosomes. Analysis of CD150 isoforms differential expression revealed that regardless of CD150 cell surface expression the mCD150 isoform with two ITSM signaling motifs was a predominant CD150 isoform in CLL B cells. The majority of CLL cases had significantly elevated expression level of the soluble sCD150, moreover CLL B cells secrete this isoform. CD150 or CD180 crosslinking on CLL B cells alone led to activation of Akt, mTORC1, ERK1/2, p38MAPK and JNK1/2 networks. Both CD150 and CD180 target the translation machinery through mTOR independent as well as mTOR dependent pathways. Moreover, both these receptors transmit pro-survival signals via Akt-mediated inhibition of GSK3β and FOXO1/FOXO3a. Unexpectedly, coligation CD150 and CD180 receptors on CLL B cells led to mutual inhibition of the Akt and MAPK pathways. While CD150 and CD180 coligation resulted in reduced phosphorylation of Akt, ERK1/2, c-Jun, RSK, p70S6K, S6RP, and 4E-BP; it led to complete blocking of mTOR and p38MAPK phosphorylation. At the same time coligation of CD150 and CD40 receptors did not result in Akt and MAPK inhibition. This suggests that combination of signals via CD150 and CD180 leads to blocking of pro-survival pathways that may be a restraining factor for neoplastic CLL B cells propagation in more than 50% of CLL cases where these receptors are coexpressed.

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Section: Discussionmentioning

confidence: 99%

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

et al. 2017

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“…As coreceptor molecule CD150 in CLL B cells can function alone or in cooperation with others cell surface receptors. Among them is CD180 that also is associated with mutational IGHV status and is involved in Akt and MAPK kinases activation [104][105][106]. CD180 is coexpressed and colocalized with CD150 on the cell surface membrane in around 60% of CLL cases.…”

Section: Cd150 Is a Candidate For Therapeutic Intervention In Leukemimentioning

confidence: 99%

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Gordiienko

Shlapatska

Kovalevska

et al. 2019

Clinical Immunology

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SLAMF1/CD150 receptor is a founder of signaling lymphocyte activation molecule (SLAM) family of cell-surface receptors. It is widely expressed on cells within hematopoietic system. In hematologic malignancies CD150 cell surface expression is restricted to cutaneous T-cell lymphomas, few types of B-cell non-Hodgkin's lymphoma, near half of cases of chronic lymphocytic leukemia, Hodgkin's lymphoma, and multiple myeloma. Differential expression among various types of hematological malignancies allows considering CD150 as diagnostical and potential prognostic marker. Moreover, CD150 may be a target for antibody-based or measles virus oncolytic therapy. Due to CD150 signaling properties it is involved in regulation of malignant cell fate decision and tumor microenvironment in Hodgkin's lymphoma and chronic lymphocytic leukemia. This review summarizes evidence for the important role of CD150 in pathogenesis of hematologic malignancies.

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“…The radioprotective 105 kDa protein (RP105) is a TLR4 homologue which lacks the intracytoplasmic Toll-IL-1 receptor (TIR) domain of TLR4 (21,22). RP105 is widely involved in the pathophysiological process of various cardiovascular diseases through directly inhibiting TLR4-driven pathogenesis during myocardial infarction, atherosclerosis and post-interventional vascular remodeling (22)(23)(24).…”

Section: Radioprotective 105 Kda Protein Attenuates Ischemia/reperfusmentioning

confidence: 99%

Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats

Guo

Jiang

Yang

et al. 2016

International Journal of Molecular Medicine

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Toll-like receptor 4 (TLR4) serves as an important inducer of apoptotic and autophagic responses in myocardial ischemia/reperfusion (I/R) injury (MIRI). Radioprotective 105 kDa protein (RP105) is a specific inhibitor of TLR4. However, the molecular mechanisms by which RP105 represses myocardial apoptosis and autophagy through TLR4‑mediated signaling during I/R have not yet been fully elucidated. Therefore, in the present study, we aimed to examine whether adenovirus-mediated RP105 overexpression repressed myocardial apoptosis and autophagy by inhibiting the TLR4-driven mechanism in MIRI. Three days after the injection of virus or saline into the myocardium, Sprague-Dawley (SD) rats were subjected to 30 min of left anterior descending coronary artery occlusion and 6 h of reperfusion. Myocardial specimens were prepared for analysis. We performed immunohistochemichal and histopathological analysis, the measurement of cardiac biomarkers, TUNEL assay , RT-qPCR and western blot analysis. The results indicated that the overexpression of RP105 contributed to an amelioration of myocardial histological damage, decreased leakage of creatine kinase (CK) and lactate dehydrogenase (LDH), as well as a reduction in the number of TUNEL-positive cardiomyocytes. The levels of positively associated modulators of apoptosis and autophagy were also significantly downregulated by RP105, whereas Bcl-2, which plays an opposite role in inducing apoptosis and autophagy, was inversely upregulated. Furthermore, the overexpression of RP105 led to the repression of TLR4 activity and the phosphorylation of NF-κB/p65, as well as the reduced production of the cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). Taken together, these data suggest that RP105 protects the myocardium against apoptosis and autophagy, and plays a cardioprotective role during I/R injury. This is most likely due to the inactivation of TLR4/NF-κB signaling pathway. Thus, RP105 may represent an innovative therapeutic target for attenuating MIRI.

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Rewiring of sIgM-Mediated Intracellular Signaling through the CD180 Toll-like Receptor

Cited by 12 publications

References 66 publications

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

The interplay of CD150 and CD180 receptor pathways contribute to the pathobiology of chronic lymphocytic leukemia B cells by selective inhibition of Akt and MAPK signaling

SLAMF1/CD150 in hematologic malignancies: Silent marker or active player?

Radioprotective 105 kDa protein attenuates ischemia/reperfusion-induced myocardial apoptosis and autophagy by inhibiting the activation of the TLR4/NF-κB signaling pathway in rats

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