The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling
Signalling of interleukin (IL)-6 and interleukin-11 through gp130 homodimeric receptor complexes has been analysed with respect to initiation and termination of signalling in great detail. Gp130 contains a crucial motif around tyrosine Y759, which mediates negative regulation through the feedback in...
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| Veröffentlicht in: | Cellular signalling 2005-05, Vol.17 (5), p.559-569 |
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| creator | Clahsen, Thomas Lehmann, Ute Stross, Claudia Hermanns, Heike M. Volkmer-Engert, Rudolf Schneider-Mergener, Jens Heinrich, Peter C. Schaper, Fred |
| description | Signalling of interleukin (IL)-6 and interleukin-11 through gp130 homodimeric receptor complexes has been analysed with respect to initiation and termination of signalling in great detail. Gp130 contains a crucial motif around tyrosine Y759, which mediates negative regulation through the feedback inhibitor SOCS3 and the protein tyrosine phosphatase SHP2. Signalling of leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), CT-1-like factor (CLC) or oncostatin M (OSM) through gp130/LIF-R is believed to be similar due to the presence of the common signal transducer gp130 within the receptor complexes utilized, but the difference in the composition of gp130/gp130-homodimers and gp130/LIF-R-heterodimers is likely to be reflected in different signalling. Here, we analysed the contribution of the LIF-R within the gp130/LIF-R complex to negative regulation mediated by SHP2 and SOCS3. We show that SHP2 contributes to the negative regulation of signalling through gp130/LIF-R complexes. The inhibitory tyrosine motifs within the cytoplasmic parts of gp130 and the LIF-R act independently. Whereas SHP2 and SOCS3 bind directly to the inhibitory motif of gp130, only SHP2 was found to bind to the corresponding inhibitory sequence of the LIF-R. This observation was further corroborated by experiments indicating that mainly gp130 contributes to the inhibition of signalling by SOCS3. |
| doi_str_mv | 10.1016/j.cellsig.2004.09.016 |
| format | Article |
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Gp130 contains a crucial motif around tyrosine Y759, which mediates negative regulation through the feedback inhibitor SOCS3 and the protein tyrosine phosphatase SHP2. Signalling of leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), CT-1-like factor (CLC) or oncostatin M (OSM) through gp130/LIF-R is believed to be similar due to the presence of the common signal transducer gp130 within the receptor complexes utilized, but the difference in the composition of gp130/gp130-homodimers and gp130/LIF-R-heterodimers is likely to be reflected in different signalling. Here, we analysed the contribution of the LIF-R within the gp130/LIF-R complex to negative regulation mediated by SHP2 and SOCS3. We show that SHP2 contributes to the negative regulation of signalling through gp130/LIF-R complexes. The inhibitory tyrosine motifs within the cytoplasmic parts of gp130 and the LIF-R act independently. Whereas SHP2 and SOCS3 bind directly to the inhibitory motif of gp130, only SHP2 was found to bind to the corresponding inhibitory sequence of the LIF-R. This observation was further corroborated by experiments indicating that mainly gp130 contributes to the inhibition of signalling by SOCS3.</description><identifier>ISSN: 0898-6568</identifier><identifier>EISSN: 1873-3913</identifier><identifier>DOI: 10.1016/j.cellsig.2004.09.016</identifier><identifier>PMID: 15683731</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Amino Acid Motifs ; Animals ; Antigens, CD - chemistry ; Antigens, CD - metabolism ; Cytokine Receptor gp130 ; Down-Regulation ; gp130 ; Humans ; IL-6-type cytokines ; Intracellular Signaling Peptides and Proteins ; Leukemia Inhibitory Factor Receptor alpha Subunit ; LIFR ; Membrane Glycoproteins - chemistry ; Membrane Glycoproteins - metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatases - metabolism ; Receptor ; Receptors, Cytokine - chemistry ; Receptors, Cytokine - metabolism ; Receptors, OSM-LIF ; Repressor Proteins - metabolism ; SHP2 ; Signal Transduction ; SOCS3 ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; Transcription Factors - metabolism ; Tyrosine - metabolism</subject><ispartof>Cellular signalling, 2005-05, Vol.17 (5), p.559-569</ispartof><rights>2004 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c363t-ea5a0347be564cc687cff0807eedd9b1afada491ca65414be98329ee92be0a5e3</citedby><cites>FETCH-LOGICAL-c363t-ea5a0347be564cc687cff0807eedd9b1afada491ca65414be98329ee92be0a5e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cellsig.2004.09.016$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15683731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Clahsen, Thomas</creatorcontrib><creatorcontrib>Lehmann, Ute</creatorcontrib><creatorcontrib>Stross, Claudia</creatorcontrib><creatorcontrib>Hermanns, Heike M.</creatorcontrib><creatorcontrib>Volkmer-Engert, Rudolf</creatorcontrib><creatorcontrib>Schneider-Mergener, Jens</creatorcontrib><creatorcontrib>Heinrich, Peter C.</creatorcontrib><creatorcontrib>Schaper, Fred</creatorcontrib><title>The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling</title><title>Cellular signalling</title><addtitle>Cell Signal</addtitle><description>Signalling of interleukin (IL)-6 and interleukin-11 through gp130 homodimeric receptor complexes has been analysed with respect to initiation and termination of signalling in great detail. Gp130 contains a crucial motif around tyrosine Y759, which mediates negative regulation through the feedback inhibitor SOCS3 and the protein tyrosine phosphatase SHP2. Signalling of leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), CT-1-like factor (CLC) or oncostatin M (OSM) through gp130/LIF-R is believed to be similar due to the presence of the common signal transducer gp130 within the receptor complexes utilized, but the difference in the composition of gp130/gp130-homodimers and gp130/LIF-R-heterodimers is likely to be reflected in different signalling. Here, we analysed the contribution of the LIF-R within the gp130/LIF-R complex to negative regulation mediated by SHP2 and SOCS3. We show that SHP2 contributes to the negative regulation of signalling through gp130/LIF-R complexes. The inhibitory tyrosine motifs within the cytoplasmic parts of gp130 and the LIF-R act independently. Whereas SHP2 and SOCS3 bind directly to the inhibitory motif of gp130, only SHP2 was found to bind to the corresponding inhibitory sequence of the LIF-R. This observation was further corroborated by experiments indicating that mainly gp130 contributes to the inhibition of signalling by SOCS3.</description><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Antigens, CD - chemistry</subject><subject>Antigens, CD - metabolism</subject><subject>Cytokine Receptor gp130</subject><subject>Down-Regulation</subject><subject>gp130</subject><subject>Humans</subject><subject>IL-6-type cytokines</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Leukemia Inhibitory Factor Receptor alpha Subunit</subject><subject>LIFR</subject><subject>Membrane Glycoproteins - chemistry</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Protein Tyrosine Phosphatase, Non-Receptor Type 11</subject><subject>Protein Tyrosine Phosphatases - metabolism</subject><subject>Receptor</subject><subject>Receptors, Cytokine - chemistry</subject><subject>Receptors, Cytokine - metabolism</subject><subject>Receptors, OSM-LIF</subject><subject>Repressor Proteins - metabolism</subject><subject>SHP2</subject><subject>Signal Transduction</subject><subject>SOCS3</subject><subject>Suppressor of Cytokine Signaling 3 Protein</subject><subject>Suppressor of Cytokine Signaling Proteins</subject><subject>Transcription Factors - metabolism</subject><subject>Tyrosine - metabolism</subject><issn>0898-6568</issn><issn>1873-3913</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u3CAUhVGVqplO-wiNWGVn5zLY2KyiKGrSSCNVqtI1wvjaw8g2DjBJ5wXy3GV-pC67Ag7nngvfJeQbg5wBEzfb3OAwBNvnK4AiB5kn9QNZsLriGZeMX5AF1LLORCnqS_I5hC0AK0GsPpFLljRecbYg788bpHHvXbATUlkV9M3GjZ1oTPr66SH7lZmNTmfXHaV-Zhxujhd0gxG9G9FbQz0anKPz1LhxHvAPHbG1OmKgE_Y62ldMln43pK07hqUIml4_6WGwU_-FfOz0EPDreV2S3w_fn-9_ZOufj0_3d-vMcMFjhrrUwIuqwVIUxoi6Ml0HNVSIbSsbpjvd6kIyo0VZsKJBWfOVRJSrBkGXyJfk-pQ7e_eywxDVaMMBpJ7Q7YISFZcgEpolKU9Gk9AEj52avR213ysG6jAAtVXnAajDABRIldRUd3VusGsSgn9VZ-LJcHsyYPrmq0WvgrE4mYQrMYyqdfY_Lf4C5Iia4w</recordid><startdate>20050501</startdate><enddate>20050501</enddate><creator>Clahsen, Thomas</creator><creator>Lehmann, Ute</creator><creator>Stross, Claudia</creator><creator>Hermanns, Heike M.</creator><creator>Volkmer-Engert, Rudolf</creator><creator>Schneider-Mergener, Jens</creator><creator>Heinrich, Peter C.</creator><creator>Schaper, Fred</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20050501</creationdate><title>The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling</title><author>Clahsen, Thomas ; Lehmann, Ute ; Stross, Claudia ; Hermanns, Heike M. ; Volkmer-Engert, Rudolf ; Schneider-Mergener, Jens ; Heinrich, Peter C. ; Schaper, Fred</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c363t-ea5a0347be564cc687cff0807eedd9b1afada491ca65414be98329ee92be0a5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Amino Acid Motifs</topic><topic>Animals</topic><topic>Antigens, CD - chemistry</topic><topic>Antigens, CD - metabolism</topic><topic>Cytokine Receptor gp130</topic><topic>Down-Regulation</topic><topic>gp130</topic><topic>Humans</topic><topic>IL-6-type cytokines</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Leukemia Inhibitory Factor Receptor alpha Subunit</topic><topic>LIFR</topic><topic>Membrane Glycoproteins - chemistry</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Protein Tyrosine Phosphatase, Non-Receptor Type 11</topic><topic>Protein Tyrosine Phosphatases - metabolism</topic><topic>Receptor</topic><topic>Receptors, Cytokine - chemistry</topic><topic>Receptors, Cytokine - metabolism</topic><topic>Receptors, OSM-LIF</topic><topic>Repressor Proteins - metabolism</topic><topic>SHP2</topic><topic>Signal Transduction</topic><topic>SOCS3</topic><topic>Suppressor of Cytokine Signaling 3 Protein</topic><topic>Suppressor of Cytokine Signaling Proteins</topic><topic>Transcription Factors - metabolism</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Clahsen, Thomas</creatorcontrib><creatorcontrib>Lehmann, Ute</creatorcontrib><creatorcontrib>Stross, Claudia</creatorcontrib><creatorcontrib>Hermanns, Heike M.</creatorcontrib><creatorcontrib>Volkmer-Engert, Rudolf</creatorcontrib><creatorcontrib>Schneider-Mergener, Jens</creatorcontrib><creatorcontrib>Heinrich, Peter C.</creatorcontrib><creatorcontrib>Schaper, Fred</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>Cellular signalling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Clahsen, Thomas</au><au>Lehmann, Ute</au><au>Stross, Claudia</au><au>Hermanns, Heike M.</au><au>Volkmer-Engert, Rudolf</au><au>Schneider-Mergener, Jens</au><au>Heinrich, Peter C.</au><au>Schaper, Fred</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling</atitle><jtitle>Cellular signalling</jtitle><addtitle>Cell Signal</addtitle><date>2005-05-01</date><risdate>2005</risdate><volume>17</volume><issue>5</issue><spage>559</spage><epage>569</epage><pages>559-569</pages><issn>0898-6568</issn><eissn>1873-3913</eissn><abstract>Signalling of interleukin (IL)-6 and interleukin-11 through gp130 homodimeric receptor complexes has been analysed with respect to initiation and termination of signalling in great detail. Gp130 contains a crucial motif around tyrosine Y759, which mediates negative regulation through the feedback inhibitor SOCS3 and the protein tyrosine phosphatase SHP2. Signalling of leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), CT-1-like factor (CLC) or oncostatin M (OSM) through gp130/LIF-R is believed to be similar due to the presence of the common signal transducer gp130 within the receptor complexes utilized, but the difference in the composition of gp130/gp130-homodimers and gp130/LIF-R-heterodimers is likely to be reflected in different signalling. Here, we analysed the contribution of the LIF-R within the gp130/LIF-R complex to negative regulation mediated by SHP2 and SOCS3. We show that SHP2 contributes to the negative regulation of signalling through gp130/LIF-R complexes. The inhibitory tyrosine motifs within the cytoplasmic parts of gp130 and the LIF-R act independently. Whereas SHP2 and SOCS3 bind directly to the inhibitory motif of gp130, only SHP2 was found to bind to the corresponding inhibitory sequence of the LIF-R. This observation was further corroborated by experiments indicating that mainly gp130 contributes to the inhibition of signalling by SOCS3.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>15683731</pmid><doi>10.1016/j.cellsig.2004.09.016</doi><tpages>11</tpages></addata></record> |
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| ispartof | Cellular signalling, 2005-05, Vol.17 (5), p.559-569 |
| issn | 0898-6568 1873-3913 |
| language | eng |
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| subjects | Amino Acid Motifs Animals Antigens, CD - chemistry Antigens, CD - metabolism Cytokine Receptor gp130 Down-Regulation gp130 Humans IL-6-type cytokines Intracellular Signaling Peptides and Proteins Leukemia Inhibitory Factor Receptor alpha Subunit LIFR Membrane Glycoproteins - chemistry Membrane Glycoproteins - metabolism Protein Tyrosine Phosphatase, Non-Receptor Type 11 Protein Tyrosine Phosphatases - metabolism Receptor Receptors, Cytokine - chemistry Receptors, Cytokine - metabolism Receptors, OSM-LIF Repressor Proteins - metabolism SHP2 Signal Transduction SOCS3 Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Transcription Factors - metabolism Tyrosine - metabolism |
| title | The tyrosine 974 within the LIF-R-chain of the gp130/LIF-R heteromeric receptor complex mediates negative regulation of LIF signalling |
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