RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells
RhoH is an atypical small G protein with defective GTPase activity that is specifically expressed in hematopoietic lineage cells. RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the...
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| Veröffentlicht in: | The Journal of immunology (1950) 2009-01, Vol.182 (2), p.957-962 |
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| container_title | The Journal of immunology (1950) |
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| creator | Oda, Hiroyo Fujimoto, Manabu Patrick, Michael S Chida, Dai Sato, Yoshinori Azuma, Yoshinao Aoki, Hiroki Abe, Takaya Suzuki, Harumi Shirai, Mutsunori |
| description | RhoH is an atypical small G protein with defective GTPase activity that is specifically expressed in hematopoietic lineage cells. RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the present study, we investigated the role of RhoH in mast cells by generating RhoH knockout mice. Despite observing normal development of mast cells in vivo, passive systemic anaphylaxis and histamine release were impaired in these mice. We also observed defective degranulation and cytokine production upon FcepsilonRI ligation in RhoH-deficient bone marrow-derived mast cells. Furthermore, FcepsilonRI-dependent activation of Syk and phosphorylation of its downstream targets, including LAT, SLP76, PLCgamma1, and PLCgamma2 were impaired, however phosphorylation of the gamma-subunit of FcepsilonRI remained intact. We also found RhoH-Syk association that was greatly enhanced by active Fyn. Our results indicate that RhoH regulates FcepsilonRI signaling in mast cells by facilitating Syk activation, possibly as an adaptor molecule for Syk. |
| doi_str_mv | 10.4049/jimmunol.182.2.957 |
| format | Article |
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RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the present study, we investigated the role of RhoH in mast cells by generating RhoH knockout mice. Despite observing normal development of mast cells in vivo, passive systemic anaphylaxis and histamine release were impaired in these mice. We also observed defective degranulation and cytokine production upon FcepsilonRI ligation in RhoH-deficient bone marrow-derived mast cells. Furthermore, FcepsilonRI-dependent activation of Syk and phosphorylation of its downstream targets, including LAT, SLP76, PLCgamma1, and PLCgamma2 were impaired, however phosphorylation of the gamma-subunit of FcepsilonRI remained intact. We also found RhoH-Syk association that was greatly enhanced by active Fyn. Our results indicate that RhoH regulates FcepsilonRI signaling in mast cells by facilitating Syk activation, possibly as an adaptor molecule for Syk.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.182.2.957</identifier><identifier>PMID: 19124738</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Cell Degranulation - genetics ; Cell Degranulation - immunology ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cells, Cultured ; Enzyme Activation - immunology ; Intracellular Signaling Peptides and Proteins - metabolism ; Mast Cells - cytology ; Mast Cells - enzymology ; Mast Cells - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Passive Cutaneous Anaphylaxis - genetics ; Passive Cutaneous Anaphylaxis - immunology ; Protein-Tyrosine Kinases - metabolism ; Receptors, IgE - physiology ; rho GTP-Binding Proteins - biosynthesis ; rho GTP-Binding Proteins - deficiency ; rho GTP-Binding Proteins - genetics ; rho GTP-Binding Proteins - physiology ; Signal Transduction - immunology ; Syk Kinase ; Transcription Factors - biosynthesis ; Transcription Factors - deficiency ; Transcription Factors - genetics ; Transcription Factors - physiology</subject><ispartof>The Journal of immunology (1950), 2009-01, Vol.182 (2), p.957-962</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c345t-aa4923170c8efb47431eb9a588e02e707b73129b0ae07d75cdef73e9878c31e3</citedby><cites>FETCH-LOGICAL-c345t-aa4923170c8efb47431eb9a588e02e707b73129b0ae07d75cdef73e9878c31e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19124738$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oda, Hiroyo</creatorcontrib><creatorcontrib>Fujimoto, Manabu</creatorcontrib><creatorcontrib>Patrick, Michael S</creatorcontrib><creatorcontrib>Chida, Dai</creatorcontrib><creatorcontrib>Sato, Yoshinori</creatorcontrib><creatorcontrib>Azuma, Yoshinao</creatorcontrib><creatorcontrib>Aoki, Hiroki</creatorcontrib><creatorcontrib>Abe, Takaya</creatorcontrib><creatorcontrib>Suzuki, Harumi</creatorcontrib><creatorcontrib>Shirai, Mutsunori</creatorcontrib><title>RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>RhoH is an atypical small G protein with defective GTPase activity that is specifically expressed in hematopoietic lineage cells. RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the present study, we investigated the role of RhoH in mast cells by generating RhoH knockout mice. Despite observing normal development of mast cells in vivo, passive systemic anaphylaxis and histamine release were impaired in these mice. We also observed defective degranulation and cytokine production upon FcepsilonRI ligation in RhoH-deficient bone marrow-derived mast cells. Furthermore, FcepsilonRI-dependent activation of Syk and phosphorylation of its downstream targets, including LAT, SLP76, PLCgamma1, and PLCgamma2 were impaired, however phosphorylation of the gamma-subunit of FcepsilonRI remained intact. We also found RhoH-Syk association that was greatly enhanced by active Fyn. Our results indicate that RhoH regulates FcepsilonRI signaling in mast cells by facilitating Syk activation, possibly as an adaptor molecule for Syk.</description><subject>Animals</subject><subject>Cell Degranulation - genetics</subject><subject>Cell Degranulation - immunology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation - immunology</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Mast Cells - cytology</subject><subject>Mast Cells - enzymology</subject><subject>Mast Cells - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Passive Cutaneous Anaphylaxis - genetics</subject><subject>Passive Cutaneous Anaphylaxis - immunology</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Receptors, IgE - physiology</subject><subject>rho GTP-Binding Proteins - biosynthesis</subject><subject>rho GTP-Binding Proteins - deficiency</subject><subject>rho GTP-Binding Proteins - genetics</subject><subject>rho GTP-Binding Proteins - physiology</subject><subject>Signal Transduction - immunology</subject><subject>Syk Kinase</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - deficiency</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1Kw0AYRQdRbK2-gAuZlbvEb36SSZZSrC0UhFLcDpPJF52SPzPJom_vlFZc3c25l8sh5JFBLEHmLwfXNFPb1THLeMzjPFFXZM6SBKI0hfSazAE4j5hK1YzceX8AgBS4vCUzljMulcjm5HP33a1pX5ujp3Zwo7OmpkNXo6eupStLsfeu7lq620Ql9tiW2I7Uu682cONgWl9OdnQBCHhj_Egt1rW_JzeVqT0-XHJB9qu3_XIdbT_eN8vXbWSFTMbIGJlzwRTYDKtCKikYFrlJsgyBowJVKMF4XoBBUKVKbImVEphnKrMBFQvyfJ7th-5nQj_qxvnTAdNiN3mdpipnICGA_AzaofN-wEr3g2vMcNQM9Emm_pOpg0zNdZAZSk-X9alosPyvXOyJX9gEcts</recordid><startdate>20090115</startdate><enddate>20090115</enddate><creator>Oda, Hiroyo</creator><creator>Fujimoto, Manabu</creator><creator>Patrick, Michael S</creator><creator>Chida, Dai</creator><creator>Sato, Yoshinori</creator><creator>Azuma, Yoshinao</creator><creator>Aoki, Hiroki</creator><creator>Abe, Takaya</creator><creator>Suzuki, Harumi</creator><creator>Shirai, Mutsunori</creator><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>7X8</scope></search><sort><creationdate>20090115</creationdate><title>RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells</title><author>Oda, Hiroyo ; Fujimoto, Manabu ; Patrick, Michael S ; Chida, Dai ; Sato, Yoshinori ; Azuma, Yoshinao ; Aoki, Hiroki ; Abe, Takaya ; Suzuki, Harumi ; Shirai, Mutsunori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c345t-aa4923170c8efb47431eb9a588e02e707b73129b0ae07d75cdef73e9878c31e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Cell Degranulation - genetics</topic><topic>Cell Degranulation - immunology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Enzyme Activation - immunology</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Mast Cells - cytology</topic><topic>Mast Cells - enzymology</topic><topic>Mast Cells - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Passive Cutaneous Anaphylaxis - genetics</topic><topic>Passive Cutaneous Anaphylaxis - immunology</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Receptors, IgE - physiology</topic><topic>rho GTP-Binding Proteins - biosynthesis</topic><topic>rho GTP-Binding Proteins - deficiency</topic><topic>rho GTP-Binding Proteins - genetics</topic><topic>rho GTP-Binding Proteins - physiology</topic><topic>Signal Transduction - immunology</topic><topic>Syk Kinase</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - deficiency</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oda, Hiroyo</creatorcontrib><creatorcontrib>Fujimoto, Manabu</creatorcontrib><creatorcontrib>Patrick, Michael S</creatorcontrib><creatorcontrib>Chida, Dai</creatorcontrib><creatorcontrib>Sato, Yoshinori</creatorcontrib><creatorcontrib>Azuma, Yoshinao</creatorcontrib><creatorcontrib>Aoki, Hiroki</creatorcontrib><creatorcontrib>Abe, Takaya</creatorcontrib><creatorcontrib>Suzuki, Harumi</creatorcontrib><creatorcontrib>Shirai, Mutsunori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oda, Hiroyo</au><au>Fujimoto, Manabu</au><au>Patrick, Michael S</au><au>Chida, Dai</au><au>Sato, Yoshinori</au><au>Azuma, Yoshinao</au><au>Aoki, Hiroki</au><au>Abe, Takaya</au><au>Suzuki, Harumi</au><au>Shirai, Mutsunori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2009-01-15</date><risdate>2009</risdate><volume>182</volume><issue>2</issue><spage>957</spage><epage>962</epage><pages>957-962</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>RhoH is an atypical small G protein with defective GTPase activity that is specifically expressed in hematopoietic lineage cells. RhoH has been implicated in regulation of several physiological processes including hematopoiesis, integrin activation, and T cell differentiation and activation. In the present study, we investigated the role of RhoH in mast cells by generating RhoH knockout mice. Despite observing normal development of mast cells in vivo, passive systemic anaphylaxis and histamine release were impaired in these mice. We also observed defective degranulation and cytokine production upon FcepsilonRI ligation in RhoH-deficient bone marrow-derived mast cells. Furthermore, FcepsilonRI-dependent activation of Syk and phosphorylation of its downstream targets, including LAT, SLP76, PLCgamma1, and PLCgamma2 were impaired, however phosphorylation of the gamma-subunit of FcepsilonRI remained intact. We also found RhoH-Syk association that was greatly enhanced by active Fyn. Our results indicate that RhoH regulates FcepsilonRI signaling in mast cells by facilitating Syk activation, possibly as an adaptor molecule for Syk.</abstract><cop>United States</cop><pmid>19124738</pmid><doi>10.4049/jimmunol.182.2.957</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cell Degranulation - genetics Cell Degranulation - immunology Cell Differentiation - genetics Cell Differentiation - immunology Cells, Cultured Enzyme Activation - immunology Intracellular Signaling Peptides and Proteins - metabolism Mast Cells - cytology Mast Cells - enzymology Mast Cells - immunology Mice Mice, Inbred C57BL Mice, Knockout Passive Cutaneous Anaphylaxis - genetics Passive Cutaneous Anaphylaxis - immunology Protein-Tyrosine Kinases - metabolism Receptors, IgE - physiology rho GTP-Binding Proteins - biosynthesis rho GTP-Binding Proteins - deficiency rho GTP-Binding Proteins - genetics rho GTP-Binding Proteins - physiology Signal Transduction - immunology Syk Kinase Transcription Factors - biosynthesis Transcription Factors - deficiency Transcription Factors - genetics Transcription Factors - physiology |
| title | RhoH plays critical roles in Fc epsilon RI-dependent signal transduction in mast cells |
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