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A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells
Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activati...
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Published in: | BMC immunology 2001-06, Vol.2 (1), p.4-4, Article 4 |
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description | Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-gamma2 (PLCgamma2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCgamma2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCgamma2-deficient DT40 B cell line.
Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCgamma2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCgamma2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCgamma2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis.
These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCgamma2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types. |
doi_str_mv | 10.1186/1471-2172-2-4 |
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Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCgamma2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCgamma2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCgamma2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis.
These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCgamma2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types.</description><identifier>ISSN: 1471-2172</identifier><identifier>EISSN: 1471-2172</identifier><identifier>DOI: 10.1186/1471-2172-2-4</identifier><identifier>PMID: 11410123</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Agammaglobulinaemia Tyrosine Kinase ; Animals ; Antigens ; Apoptosis ; B cells ; B-Lymphocytes - enzymology ; B-Lymphocytes - immunology ; Calcium Signaling ; Cell Line ; Cellular signal transduction ; Estrogen ; Immune response ; MAP Kinase Signaling System ; Medical research ; Medicine, Experimental ; Mice ; Mitogens ; Mutation ; Phenols ; Phospholipase C gamma ; Phospholipases ; Phosphotransferases ; Physiological aspects ; Protein kinases ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Receptors, Estrogen - genetics ; Recombinant Fusion Proteins - metabolism ; Signal Transduction ; Type C Phospholipases - genetics ; Type C Phospholipases - physiology ; Tyrosine</subject><ispartof>BMC immunology, 2001-06, Vol.2 (1), p.4-4, Article 4</ispartof><rights>COPYRIGHT 2001 BioMed Central Ltd.</rights><rights>Copyright © 2001 Tomlinson et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. 2001 Tomlinson et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b6504-63391f1086810d2181584e09b27605ede2fa9228cd3dff06a3ff8e8671cfc6893</citedby><cites>FETCH-LOGICAL-b6504-63391f1086810d2181584e09b27605ede2fa9228cd3dff06a3ff8e8671cfc6893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC32313/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC32313/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11410123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomlinson, M G</creatorcontrib><creatorcontrib>Woods, D B</creatorcontrib><creatorcontrib>McMahon, M</creatorcontrib><creatorcontrib>Wahl, M I</creatorcontrib><creatorcontrib>Witte, O N</creatorcontrib><creatorcontrib>Kurosaki, T</creatorcontrib><creatorcontrib>Bolen, J B</creatorcontrib><creatorcontrib>Johnston, J A</creatorcontrib><title>A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells</title><title>BMC immunology</title><addtitle>BMC Immunol</addtitle><description>Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-gamma2 (PLCgamma2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCgamma2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCgamma2-deficient DT40 B cell line.
Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCgamma2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCgamma2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCgamma2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis.
These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCgamma2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types.</description><subject>Agammaglobulinaemia Tyrosine Kinase</subject><subject>Animals</subject><subject>Antigens</subject><subject>Apoptosis</subject><subject>B cells</subject><subject>B-Lymphocytes - enzymology</subject><subject>B-Lymphocytes - immunology</subject><subject>Calcium Signaling</subject><subject>Cell Line</subject><subject>Cellular signal transduction</subject><subject>Estrogen</subject><subject>Immune response</subject><subject>MAP Kinase Signaling System</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Mice</subject><subject>Mitogens</subject><subject>Mutation</subject><subject>Phenols</subject><subject>Phospholipase C gamma</subject><subject>Phospholipases</subject><subject>Phosphotransferases</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Receptors, Estrogen - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>Signal Transduction</subject><subject>Type C Phospholipases - genetics</subject><subject>Type C Phospholipases - physiology</subject><subject>Tyrosine</subject><issn>1471-2172</issn><issn>1471-2172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqFk11rFDEYhQdRbK1eeisBQfFiat4kM5OBXrhdtC4sKH5ch2wm2abOJOsks3X_gr_ajLvUDiolhHw95xDOm2TZU8CnALx8DayCnEBFcpKze9nxzfr-rflR9iiEK4yh4oQ_zI4AGGAg9Dj7OUPKu8ZG651skfF9h7xB5_0QvXsZUNz1Plin0TfrZNDIBhQGY6yy2kUUPZIq2q2MGnVDG-2m1ajx1y7EXssOBbtOrtat0UbGy2u5C2hrJfq4nKML2XUSEWQdOkdKt214nD0wsg36yWE8yb6-e_tl_j5ffrhYzGfLfFUWmOUlpTUYwLzkgBsCHArONK5XpCpxoRtNjKwJ4aqhjTG4lNQYrnlZgTKq5DU9yRZ738bLK7HpbSf7nfDSit8bvl8L2UerWi1IQQtWKNPoumaMYV4XipKSclNBXTdl8jrbe22GVacblULpZTsxnZ44eynWfisooUCT_M1evrL-P_LpifKdGKsqxqoKIliyeHG4Qe-_DzpE0dkw5imd9kMQFdAKgPA7QagZTR3fDVac4aIaHZ_vwbVMWVlnfLqjGmEx45iUqR68SNTpP6jUGt3Z9Pa0sWl_Ing1ESQm6h9xLYcQxOLzpymb71mVnmnotbnJDrAY_8dfaT27Xa8_9OFD0F8yewk8</recordid><startdate>20010608</startdate><enddate>20010608</enddate><creator>Tomlinson, M G</creator><creator>Woods, D B</creator><creator>McMahon, M</creator><creator>Wahl, M I</creator><creator>Witte, O N</creator><creator>Kurosaki, T</creator><creator>Bolen, J B</creator><creator>Johnston, J A</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</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>ISR</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20010608</creationdate><title>A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells</title><author>Tomlinson, M G ; Woods, D B ; McMahon, M ; Wahl, M I ; Witte, O N ; Kurosaki, T ; Bolen, J B ; Johnston, J A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b6504-63391f1086810d2181584e09b27605ede2fa9228cd3dff06a3ff8e8671cfc6893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Agammaglobulinaemia Tyrosine Kinase</topic><topic>Animals</topic><topic>Antigens</topic><topic>Apoptosis</topic><topic>B cells</topic><topic>B-Lymphocytes - enzymology</topic><topic>B-Lymphocytes - immunology</topic><topic>Calcium Signaling</topic><topic>Cell Line</topic><topic>Cellular signal transduction</topic><topic>Estrogen</topic><topic>Immune response</topic><topic>MAP Kinase Signaling System</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Mice</topic><topic>Mitogens</topic><topic>Mutation</topic><topic>Phenols</topic><topic>Phospholipase C gamma</topic><topic>Phospholipases</topic><topic>Phosphotransferases</topic><topic>Physiological aspects</topic><topic>Protein kinases</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Receptors, Estrogen - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>Signal Transduction</topic><topic>Type C Phospholipases - genetics</topic><topic>Type C Phospholipases - physiology</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomlinson, M G</creatorcontrib><creatorcontrib>Woods, D B</creatorcontrib><creatorcontrib>McMahon, M</creatorcontrib><creatorcontrib>Wahl, M I</creatorcontrib><creatorcontrib>Witte, O N</creatorcontrib><creatorcontrib>Kurosaki, T</creatorcontrib><creatorcontrib>Bolen, J B</creatorcontrib><creatorcontrib>Johnston, J A</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: Science</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>BMC immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tomlinson, M G</au><au>Woods, D B</au><au>McMahon, M</au><au>Wahl, M I</au><au>Witte, O N</au><au>Kurosaki, T</au><au>Bolen, J B</au><au>Johnston, J A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells</atitle><jtitle>BMC immunology</jtitle><addtitle>BMC Immunol</addtitle><date>2001-06-08</date><risdate>2001</risdate><volume>2</volume><issue>1</issue><spage>4</spage><epage>4</epage><pages>4-4</pages><artnum>4</artnum><issn>1471-2172</issn><eissn>1471-2172</eissn><abstract>Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-gamma2 (PLCgamma2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCgamma2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCgamma2-deficient DT40 B cell line.
Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCgamma2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCgamma2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCgamma2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis.
These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCgamma2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>11410123</pmid><doi>10.1186/1471-2172-2-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Agammaglobulinaemia Tyrosine Kinase Animals Antigens Apoptosis B cells B-Lymphocytes - enzymology B-Lymphocytes - immunology Calcium Signaling Cell Line Cellular signal transduction Estrogen Immune response MAP Kinase Signaling System Medical research Medicine, Experimental Mice Mitogens Mutation Phenols Phospholipase C gamma Phospholipases Phosphotransferases Physiological aspects Protein kinases Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Receptors, Estrogen - genetics Recombinant Fusion Proteins - metabolism Signal Transduction Type C Phospholipases - genetics Type C Phospholipases - physiology Tyrosine |
title | A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells |
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