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
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...
Gespeichert in:
| Veröffentlicht in: | PloS one 2017-10, Vol.12 (10), p.e0185940-e0185940 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0185940 |
|---|---|
| container_issue | 10 |
| container_start_page | e0185940 |
| container_title | PloS one |
| container_volume | 12 |
| creator | Gordiienko, Inna Shlapatska, Larysa Kholodniuk, Valeriia Sklyarenko, Lilia Gluzman, Daniel F Clark, Edward A Sidorenko, Svetlana P |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0185940 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1991851446</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A508208856</galeid><doaj_id>oai_doaj_org_article_0c3e71006aa74fd18404020b5e5be6ce</doaj_id><sourcerecordid>A508208856</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-cc4ce2597382ee7662c0a1ac075bfe2f80195e322db08d008d08f137f7d611543</originalsourceid><addsrcrecordid>eNqNk99u0zAUxiMEYmPwBggsISG4aLGdOHFukEr5VzE0BINby3FOEm9pHGxn0GfiJbG3bmrRLlBk5cj-nc8-n32S5DHBc5IW5NWZmewg-_loBphjwlmZ4TvJISlTOsspTu_uxAfJA-fOMGYpz_P7yQHlJackKw-TP6cdID14sGMvN8g0aPmWMIzkUMeIY2RBweiNRaP03S-5cUiZwVtdTR6QN8gHgbhkKm16015qqM6aQSvUb9ZjZ9TGxximc1hrid4gBX3vULVBDnpQXl_EI3S60l6bIeYvzv3lCT4vvnxCTrehTj20D5N7jewdPNr-j5Lv79-dLj_Ojk8-rJaL45nKS-pnSmUKKCuLlFOAIs-pwpJIhQtWNUAbjknJIKW0rjCvcRy8CZY2RZ0TwrL0KHl6pTv2xomtz06QsgwukyzLA7G6Imojz8Ro9VrajTBSi8sJY1shbSi6B4FVCgXBOJeyyJqa8AxnmOKKAasgVxC0Xm93m6o11AqCubLfE91fGXQnWnMhWB6uERdB4MVWwJqfEzgv1tpFi-UAZornznjB8rLgAX32D3p7dVuqlaEAPTQm7KuiqFgwzCnmnEVqfgsVvjrccngi0Ogwv5fwci8hPiP47Vs5OSdW377-P3vyY599vsN2IHvfOdNP8TG5fTC7ApU1zllobkwmWMSeunZDxJ4S254KaU92L-gm6bqJ0r9qpBy3</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1991851446</pqid></control><display><type>article</type><title>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</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Gordiienko, Inna ; Shlapatska, Larysa ; Kholodniuk, Valeriia ; Sklyarenko, Lilia ; Gluzman, Daniel F ; Clark, Edward A ; Sidorenko, Svetlana P</creator><contributor>Gibson, Spencer B.</contributor><creatorcontrib>Gordiienko, Inna ; Shlapatska, Larysa ; Kholodniuk, Valeriia ; Sklyarenko, Lilia ; Gluzman, Daniel F ; Clark, Edward A ; Sidorenko, Svetlana P ; Gibson, Spencer B.</creatorcontrib><description>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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0185940</identifier><identifier>PMID: 28982149</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Antigens ; Antigens, CD - metabolism ; Apoptosis ; B cells ; B-Lymphocytes - metabolism ; Biology and Life Sciences ; Blood & organ donations ; c-Jun protein ; CD150 antigen ; CD18 antigen ; CD40 antigen ; Cell activation ; Cell Separation ; Cell surface ; Cell survival ; Chronic lymphocytic leukemia ; Crosslinking ; Cytoplasm ; Disease ; Endoplasmic reticulum ; Endosomes ; Epigenetics ; Flow Cytometry ; FOXO1 protein ; FOXO3 protein ; Gene expression ; Golgi apparatus ; Humans ; Immunoglobulins ; Inhibition ; Isoforms ; Kinases ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - enzymology ; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Lymphatic leukemia ; Lymphocyte receptors ; Lymphocytes B ; Machinery and equipment ; MAP kinase ; MAP Kinase Signaling System ; Measles ; Medical prognosis ; Medicine and Health Sciences ; Oncology ; Pathogenesis ; Pathology ; Patient outcomes ; Phosphatase ; Phosphorylation ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors ; Research and Analysis Methods ; Signal Transduction ; Signaling ; Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism ; Survival ; TOR protein ; Transcription factors</subject><ispartof>PloS one, 2017-10, Vol.12 (10), p.e0185940-e0185940</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Gordiienko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Gordiienko et al 2017 Gordiienko et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cc4ce2597382ee7662c0a1ac075bfe2f80195e322db08d008d08f137f7d611543</citedby><cites>FETCH-LOGICAL-c692t-cc4ce2597382ee7662c0a1ac075bfe2f80195e322db08d008d08f137f7d611543</cites><orcidid>0000-0001-8281-8006</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628907/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628907/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28982149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gibson, Spencer B.</contributor><creatorcontrib>Gordiienko, Inna</creatorcontrib><creatorcontrib>Shlapatska, Larysa</creatorcontrib><creatorcontrib>Kholodniuk, Valeriia</creatorcontrib><creatorcontrib>Sklyarenko, Lilia</creatorcontrib><creatorcontrib>Gluzman, Daniel F</creatorcontrib><creatorcontrib>Clark, Edward A</creatorcontrib><creatorcontrib>Sidorenko, Svetlana P</creatorcontrib><title>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</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>AKT protein</subject><subject>Antigens</subject><subject>Antigens, CD - metabolism</subject><subject>Apoptosis</subject><subject>B cells</subject><subject>B-Lymphocytes - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Blood & organ donations</subject><subject>c-Jun protein</subject><subject>CD150 antigen</subject><subject>CD18 antigen</subject><subject>CD40 antigen</subject><subject>Cell activation</subject><subject>Cell Separation</subject><subject>Cell surface</subject><subject>Cell survival</subject><subject>Chronic lymphocytic leukemia</subject><subject>Crosslinking</subject><subject>Cytoplasm</subject><subject>Disease</subject><subject>Endoplasmic reticulum</subject><subject>Endosomes</subject><subject>Epigenetics</subject><subject>Flow Cytometry</subject><subject>FOXO1 protein</subject><subject>FOXO3 protein</subject><subject>Gene expression</subject><subject>Golgi apparatus</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Inhibition</subject><subject>Isoforms</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - enzymology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</subject><subject>Lymphatic leukemia</subject><subject>Lymphocyte receptors</subject><subject>Lymphocytes B</subject><subject>Machinery and equipment</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System</subject><subject>Measles</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Oncology</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Patient outcomes</subject><subject>Phosphatase</subject><subject>Phosphorylation</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors</subject><subject>Research and Analysis Methods</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism</subject><subject>Survival</subject><subject>TOR protein</subject><subject>Transcription factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk99u0zAUxiMEYmPwBggsISG4aLGdOHFukEr5VzE0BINby3FOEm9pHGxn0GfiJbG3bmrRLlBk5cj-nc8-n32S5DHBc5IW5NWZmewg-_loBphjwlmZ4TvJISlTOsspTu_uxAfJA-fOMGYpz_P7yQHlJackKw-TP6cdID14sGMvN8g0aPmWMIzkUMeIY2RBweiNRaP03S-5cUiZwVtdTR6QN8gHgbhkKm16015qqM6aQSvUb9ZjZ9TGxximc1hrid4gBX3vULVBDnpQXl_EI3S60l6bIeYvzv3lCT4vvnxCTrehTj20D5N7jewdPNr-j5Lv79-dLj_Ojk8-rJaL45nKS-pnSmUKKCuLlFOAIs-pwpJIhQtWNUAbjknJIKW0rjCvcRy8CZY2RZ0TwrL0KHl6pTv2xomtz06QsgwukyzLA7G6Imojz8Ro9VrajTBSi8sJY1shbSi6B4FVCgXBOJeyyJqa8AxnmOKKAasgVxC0Xm93m6o11AqCubLfE91fGXQnWnMhWB6uERdB4MVWwJqfEzgv1tpFi-UAZornznjB8rLgAX32D3p7dVuqlaEAPTQm7KuiqFgwzCnmnEVqfgsVvjrccngi0Ogwv5fwci8hPiP47Vs5OSdW377-P3vyY599vsN2IHvfOdNP8TG5fTC7ApU1zllobkwmWMSeunZDxJ4S254KaU92L-gm6bqJ0r9qpBy3</recordid><startdate>20171005</startdate><enddate>20171005</enddate><creator>Gordiienko, Inna</creator><creator>Shlapatska, Larysa</creator><creator>Kholodniuk, Valeriia</creator><creator>Sklyarenko, Lilia</creator><creator>Gluzman, Daniel F</creator><creator>Clark, Edward A</creator><creator>Sidorenko, Svetlana P</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-8281-8006</orcidid></search><sort><creationdate>20171005</creationdate><title>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</title><author>Gordiienko, Inna ; Shlapatska, Larysa ; Kholodniuk, Valeriia ; Sklyarenko, Lilia ; Gluzman, Daniel F ; Clark, Edward A ; Sidorenko, Svetlana P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cc4ce2597382ee7662c0a1ac075bfe2f80195e322db08d008d08f137f7d611543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>AKT protein</topic><topic>Antigens</topic><topic>Antigens, CD - metabolism</topic><topic>Apoptosis</topic><topic>B cells</topic><topic>B-Lymphocytes - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Blood & organ donations</topic><topic>c-Jun protein</topic><topic>CD150 antigen</topic><topic>CD18 antigen</topic><topic>CD40 antigen</topic><topic>Cell activation</topic><topic>Cell Separation</topic><topic>Cell surface</topic><topic>Cell survival</topic><topic>Chronic lymphocytic leukemia</topic><topic>Crosslinking</topic><topic>Cytoplasm</topic><topic>Disease</topic><topic>Endoplasmic reticulum</topic><topic>Endosomes</topic><topic>Epigenetics</topic><topic>Flow Cytometry</topic><topic>FOXO1 protein</topic><topic>FOXO3 protein</topic><topic>Gene expression</topic><topic>Golgi apparatus</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Inhibition</topic><topic>Isoforms</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - enzymology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - metabolism</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</topic><topic>Lymphatic leukemia</topic><topic>Lymphocyte receptors</topic><topic>Lymphocytes B</topic><topic>Machinery and equipment</topic><topic>MAP kinase</topic><topic>MAP Kinase Signaling System</topic><topic>Measles</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Oncology</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Patient outcomes</topic><topic>Phosphatase</topic><topic>Phosphorylation</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors</topic><topic>Research and Analysis Methods</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism</topic><topic>Survival</topic><topic>TOR protein</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gordiienko, Inna</creatorcontrib><creatorcontrib>Shlapatska, Larysa</creatorcontrib><creatorcontrib>Kholodniuk, Valeriia</creatorcontrib><creatorcontrib>Sklyarenko, Lilia</creatorcontrib><creatorcontrib>Gluzman, Daniel F</creatorcontrib><creatorcontrib>Clark, Edward A</creatorcontrib><creatorcontrib>Sidorenko, Svetlana P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gordiienko, Inna</au><au>Shlapatska, Larysa</au><au>Kholodniuk, Valeriia</au><au>Sklyarenko, Lilia</au><au>Gluzman, Daniel F</au><au>Clark, Edward A</au><au>Sidorenko, Svetlana P</au><au>Gibson, Spencer B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-10-05</date><risdate>2017</risdate><volume>12</volume><issue>10</issue><spage>e0185940</spage><epage>e0185940</epage><pages>e0185940-e0185940</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28982149</pmid><doi>10.1371/journal.pone.0185940</doi><tpages>e0185940</tpages><orcidid>https://orcid.org/0000-0001-8281-8006</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-10, Vol.12 (10), p.e0185940-e0185940 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1991851446 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | AKT protein Antigens Antigens, CD - metabolism Apoptosis B cells B-Lymphocytes - metabolism Biology and Life Sciences Blood & organ donations c-Jun protein CD150 antigen CD18 antigen CD40 antigen Cell activation Cell Separation Cell surface Cell survival Chronic lymphocytic leukemia Crosslinking Cytoplasm Disease Endoplasmic reticulum Endosomes Epigenetics Flow Cytometry FOXO1 protein FOXO3 protein Gene expression Golgi apparatus Humans Immunoglobulins Inhibition Isoforms Kinases Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - enzymology Leukemia, Lymphocytic, Chronic, B-Cell - metabolism Leukemia, Lymphocytic, Chronic, B-Cell - pathology Lymphatic leukemia Lymphocyte receptors Lymphocytes B Machinery and equipment MAP kinase MAP Kinase Signaling System Measles Medical prognosis Medicine and Health Sciences Oncology Pathogenesis Pathology Patient outcomes Phosphatase Phosphorylation Prognosis Proteins Proto-Oncogene Proteins c-akt - metabolism Receptors Research and Analysis Methods Signal Transduction Signaling Signaling Lymphocytic Activation Molecule Family Member 1 - metabolism Survival TOR protein Transcription factors |
| title | 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-28T07%3A18%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20interplay%20of%20CD150%20and%20CD180%20receptor%20pathways%20contribute%20to%20the%20pathobiology%20of%20chronic%20lymphocytic%20leukemia%20B%20cells%20by%20selective%20inhibition%20of%20Akt%20and%20MAPK%20signaling&rft.jtitle=PloS%20one&rft.au=Gordiienko,%20Inna&rft.date=2017-10-05&rft.volume=12&rft.issue=10&rft.spage=e0185940&rft.epage=e0185940&rft.pages=e0185940-e0185940&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0185940&rft_dat=%3Cgale_plos_%3EA508208856%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1991851446&rft_id=info:pmid/28982149&rft_galeid=A508208856&rft_doaj_id=oai_doaj_org_article_0c3e71006aa74fd18404020b5e5be6ce&rfr_iscdi=true |