The extracellular portion of the insulin receptor β-subunit regulates the cellular trafficking of the insulin-insulin receptor complex. Studies on Chinese hamster ovary cells carrying the Cys 860 → Ser insulin receptor mutation
Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate...
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| Veröffentlicht in: | European journal of endocrinology 2003-03, Vol.148 (3), p.365-371 |
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| container_title | European journal of endocrinology |
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| creator | BENZI, L CECCHETTI, P CORDERA, R CICCARONE, A. M NOVELLI, S PAOLI, A BERTACCA, A MAFFEI, M MAGGI, D ANDRAGHETTI, G DEL PRATO, S |
| description | Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate (IRS)-1 tyrosine phosphorylation and insulin-induced metabolic and mitogenic effects. Altogether, these observations support a role of the extracellular domain of IR beta-subunit in insulin and receptor intracellular targeting as well as in insulin signaling.
This study assesses in more details the effect of IR(C860S) mutation on the trafficking of the insulin-IR complex. In particular, IR internalization, phosphorylation, dissociation and recycling, as well as insulin degradation and retroendocytosis have been investigated in CHO cells overexpressing either wild type (CHO-IR(WT)) or mutated IRs.
the C860S mutation significantly decreases IR internalization both insulin stimulated and constitutive. In spite of a similar dissociation of internalized insulin-IR complex, recycling of internalized IR was significantly faster (half life (t(1/2)): 21 min vs 40 min, P |
| doi_str_mv | 10.1530/eje.0.1480365 |
| format | Article |
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This study assesses in more details the effect of IR(C860S) mutation on the trafficking of the insulin-IR complex. In particular, IR internalization, phosphorylation, dissociation and recycling, as well as insulin degradation and retroendocytosis have been investigated in CHO cells overexpressing either wild type (CHO-IR(WT)) or mutated IRs.
the C860S mutation significantly decreases IR internalization both insulin stimulated and constitutive. In spite of a similar dissociation of internalized insulin-IR complex, recycling of internalized IR was significantly faster (half life (t(1/2)): 21 min vs 40 min, P<0.001) and more extensive (P<0.01) for IR(C860S) than for IR(WT). On the other hand, insulin degradation and retroendocytosis were superimposable in both cell lines. As expected, insulin-induced phosphorylation was similar in both IRs, however dephosphorylation was much more rapid and was greater (P<0.01) in CHO-IR(WT) as compared with CHO-IR(C860S) cells.
Transmembrane and intracellular domain of IR seem to be determinants for IR internalization. Now we report that Cys 860 in the IR beta-subunit ectodomain may be of relevance in ensuring a proper internalization and intracellular trafficking of the insulin-IR complex.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/eje.0.1480365</identifier><identifier>PMID: 12611619</identifier><language>eng</language><publisher>Colchester: Portland Press</publisher><subject>Animals ; Biological and medical sciences ; Cell receptors ; Cell structures and functions ; CHO Cells ; Cricetinae ; Extracellular Space - metabolism ; Fundamental and applied biological sciences. Psychology ; Half-Life ; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors ; Humans ; Insulin - metabolism ; Molecular and cellular biology ; Phosphorylation ; Phosphotyrosine - metabolism ; Receptor, Insulin - genetics ; Receptor, Insulin - metabolism ; Receptor, Insulin - physiology ; Transfection</subject><ispartof>European journal of endocrinology, 2003-03, Vol.148 (3), p.365-371</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-bccbbf65d4b87cec651915a5e44da6d220ebffc6adfa9e76b47fe970d2c0176b3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14631333$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12611619$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BENZI, L</creatorcontrib><creatorcontrib>CECCHETTI, P</creatorcontrib><creatorcontrib>CORDERA, R</creatorcontrib><creatorcontrib>CICCARONE, A. M</creatorcontrib><creatorcontrib>NOVELLI, S</creatorcontrib><creatorcontrib>PAOLI, A</creatorcontrib><creatorcontrib>BERTACCA, A</creatorcontrib><creatorcontrib>MAFFEI, M</creatorcontrib><creatorcontrib>MAGGI, D</creatorcontrib><creatorcontrib>ANDRAGHETTI, G</creatorcontrib><creatorcontrib>DEL PRATO, S</creatorcontrib><title>The extracellular portion of the insulin receptor β-subunit regulates the cellular trafficking of the insulin-insulin receptor complex. Studies on Chinese hamster ovary cells carrying the Cys 860 → Ser insulin receptor mutation</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate (IRS)-1 tyrosine phosphorylation and insulin-induced metabolic and mitogenic effects. Altogether, these observations support a role of the extracellular domain of IR beta-subunit in insulin and receptor intracellular targeting as well as in insulin signaling.
This study assesses in more details the effect of IR(C860S) mutation on the trafficking of the insulin-IR complex. In particular, IR internalization, phosphorylation, dissociation and recycling, as well as insulin degradation and retroendocytosis have been investigated in CHO cells overexpressing either wild type (CHO-IR(WT)) or mutated IRs.
the C860S mutation significantly decreases IR internalization both insulin stimulated and constitutive. In spite of a similar dissociation of internalized insulin-IR complex, recycling of internalized IR was significantly faster (half life (t(1/2)): 21 min vs 40 min, P<0.001) and more extensive (P<0.01) for IR(C860S) than for IR(WT). On the other hand, insulin degradation and retroendocytosis were superimposable in both cell lines. As expected, insulin-induced phosphorylation was similar in both IRs, however dephosphorylation was much more rapid and was greater (P<0.01) in CHO-IR(WT) as compared with CHO-IR(C860S) cells.
Transmembrane and intracellular domain of IR seem to be determinants for IR internalization. Now we report that Cys 860 in the IR beta-subunit ectodomain may be of relevance in ensuring a proper internalization and intracellular trafficking of the insulin-IR complex.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell receptors</subject><subject>Cell structures and functions</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Extracellular Space - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Half-Life</subject><subject>Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors</subject><subject>Humans</subject><subject>Insulin - metabolism</subject><subject>Molecular and cellular biology</subject><subject>Phosphorylation</subject><subject>Phosphotyrosine - metabolism</subject><subject>Receptor, Insulin - genetics</subject><subject>Receptor, Insulin - metabolism</subject><subject>Receptor, Insulin - physiology</subject><subject>Transfection</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNplkU9O3DAUh62qVRlol91W3pRdBjt2nGSJRm2phMQCkLqLHOeZMU3i4D-IuQAH6FE4CIfooueow4yKBN742f782U8_hD5RsqQFI0dwDctU8oowUbxBC8rLOhMV-_kWLUhFeMYFZ3to3_trQmiqyXu0R3NBqaD1Av29WAOGu-Ckgr6PvXR4si4YO2KrcUiHZvSxNyN2oGAK1uHHh8zHNo4mpL2rdCWAfyL_G5JNa6N-mfHqhSV7ZVN2mHq4W-LzEDuTTOnl1dqM4AGv5eADOGxvpds86T1W0rnNLJ6tq43HlSD4z_1vfJ7AV_YhBjk38wG907L38HE3H6DLb18vVifZ6dn3H6vj00yxqgxZq1TbalF0vK1KBUoUtKaFLIDzToouzwm0WishOy1rKEXLSw11SbpcEZqW7AAdbr2TszcRfGgG4-ePyxFs9E3JiKjysk5gtgWVs9470M3kzJDabChp5mCbFGyTym2wif-8E8d2gO6Z3iWZgC87QHole-3kqIx_5rhglKXxD255tTg</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>BENZI, L</creator><creator>CECCHETTI, P</creator><creator>CORDERA, R</creator><creator>CICCARONE, A. 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Prostaglandin receptors</topic><topic>Humans</topic><topic>Insulin - metabolism</topic><topic>Molecular and cellular biology</topic><topic>Phosphorylation</topic><topic>Phosphotyrosine - metabolism</topic><topic>Receptor, Insulin - genetics</topic><topic>Receptor, Insulin - metabolism</topic><topic>Receptor, Insulin - physiology</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BENZI, L</creatorcontrib><creatorcontrib>CECCHETTI, P</creatorcontrib><creatorcontrib>CORDERA, R</creatorcontrib><creatorcontrib>CICCARONE, A. M</creatorcontrib><creatorcontrib>NOVELLI, S</creatorcontrib><creatorcontrib>PAOLI, A</creatorcontrib><creatorcontrib>BERTACCA, A</creatorcontrib><creatorcontrib>MAFFEI, M</creatorcontrib><creatorcontrib>MAGGI, D</creatorcontrib><creatorcontrib>ANDRAGHETTI, G</creatorcontrib><creatorcontrib>DEL PRATO, S</creatorcontrib><collection>Pascal-Francis</collection><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>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BENZI, L</au><au>CECCHETTI, P</au><au>CORDERA, R</au><au>CICCARONE, A. M</au><au>NOVELLI, S</au><au>PAOLI, A</au><au>BERTACCA, A</au><au>MAFFEI, M</au><au>MAGGI, D</au><au>ANDRAGHETTI, G</au><au>DEL PRATO, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The extracellular portion of the insulin receptor β-subunit regulates the cellular trafficking of the insulin-insulin receptor complex. Studies on Chinese hamster ovary cells carrying the Cys 860 → Ser insulin receptor mutation</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2003-03-01</date><risdate>2003</risdate><volume>148</volume><issue>3</issue><spage>365</spage><epage>371</epage><pages>365-371</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate (IRS)-1 tyrosine phosphorylation and insulin-induced metabolic and mitogenic effects. Altogether, these observations support a role of the extracellular domain of IR beta-subunit in insulin and receptor intracellular targeting as well as in insulin signaling.
This study assesses in more details the effect of IR(C860S) mutation on the trafficking of the insulin-IR complex. In particular, IR internalization, phosphorylation, dissociation and recycling, as well as insulin degradation and retroendocytosis have been investigated in CHO cells overexpressing either wild type (CHO-IR(WT)) or mutated IRs.
the C860S mutation significantly decreases IR internalization both insulin stimulated and constitutive. In spite of a similar dissociation of internalized insulin-IR complex, recycling of internalized IR was significantly faster (half life (t(1/2)): 21 min vs 40 min, P<0.001) and more extensive (P<0.01) for IR(C860S) than for IR(WT). On the other hand, insulin degradation and retroendocytosis were superimposable in both cell lines. As expected, insulin-induced phosphorylation was similar in both IRs, however dephosphorylation was much more rapid and was greater (P<0.01) in CHO-IR(WT) as compared with CHO-IR(C860S) cells.
Transmembrane and intracellular domain of IR seem to be determinants for IR internalization. Now we report that Cys 860 in the IR beta-subunit ectodomain may be of relevance in ensuring a proper internalization and intracellular trafficking of the insulin-IR complex.</abstract><cop>Colchester</cop><pub>Portland Press</pub><pmid>12611619</pmid><doi>10.1530/eje.0.1480365</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of endocrinology, 2003-03, Vol.148 (3), p.365-371 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Animals Biological and medical sciences Cell receptors Cell structures and functions CHO Cells Cricetinae Extracellular Space - metabolism Fundamental and applied biological sciences. Psychology Half-Life Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors Humans Insulin - metabolism Molecular and cellular biology Phosphorylation Phosphotyrosine - metabolism Receptor, Insulin - genetics Receptor, Insulin - metabolism Receptor, Insulin - physiology Transfection |
| title | The extracellular portion of the insulin receptor β-subunit regulates the cellular trafficking of the insulin-insulin receptor complex. Studies on Chinese hamster ovary cells carrying the Cys 860 → Ser insulin receptor mutation |
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