Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes
Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor (EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) mass and a 50% increase of diac...
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| Veröffentlicht in: | The Journal of biological chemistry 1993-02, Vol.268 (5), p.3739-3746 |
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| creator | Yang, L Camoratto, A M Baffy, G Raj, S Manning, D R Williamson, J R |
| description | Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor
(EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate
(Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content
being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several
hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF
increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect
was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association
of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had
no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were
inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single
fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients.
These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism
in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis. |
| doi_str_mv | 10.1016/S0021-9258(18)53756-X |
| format | Article |
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(EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate
(Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content
being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several
hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF
increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect
was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association
of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had
no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were
inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single
fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients.
These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism
in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/S0021-9258(18)53756-X</identifier><identifier>PMID: 8429049</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Adenosine Diphosphate Ribose - metabolism ; Amino Acid Sequence ; Animals ; Antibodies ; Calcium - metabolism ; Cells, Cultured ; Diglycerides - metabolism ; Enzyme Activation ; Epidermal Growth Factor - pharmacology ; GTP-Binding Proteins - metabolism ; Inositol 1,4,5-Trisphosphate - metabolism ; Isoenzymes - metabolism ; Kinetics ; Liver - drug effects ; Liver - metabolism ; Male ; Molecular Sequence Data ; Oligopeptides - chemical synthesis ; Oligopeptides - immunology ; Pertussis Toxin ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Time Factors ; Type C Phospholipases - metabolism ; Virulence Factors, Bordetella - pharmacology</subject><ispartof>The Journal of biological chemistry, 1993-02, Vol.268 (5), p.3739-3746</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c225x-128e17d9b58d2e46946a775c925f38f879914abde89dd002e258673952fa9adf3</citedby><cites>FETCH-LOGICAL-c225x-128e17d9b58d2e46946a775c925f38f879914abde89dd002e258673952fa9adf3</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/8429049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, L</creatorcontrib><creatorcontrib>Camoratto, A M</creatorcontrib><creatorcontrib>Baffy, G</creatorcontrib><creatorcontrib>Raj, S</creatorcontrib><creatorcontrib>Manning, D R</creatorcontrib><creatorcontrib>Williamson, J R</creatorcontrib><title>Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor
(EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate
(Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content
being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several
hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF
increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect
was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association
of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had
no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were
inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single
fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients.
These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism
in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis.</description><subject>Adenosine Diphosphate Ribose - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Calcium - metabolism</subject><subject>Cells, Cultured</subject><subject>Diglycerides - metabolism</subject><subject>Enzyme Activation</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Inositol 1,4,5-Trisphosphate - metabolism</subject><subject>Isoenzymes - metabolism</subject><subject>Kinetics</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Molecular Sequence Data</subject><subject>Oligopeptides - chemical synthesis</subject><subject>Oligopeptides - immunology</subject><subject>Pertussis Toxin</subject><subject>Phosphorylation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Time Factors</subject><subject>Type C Phospholipases - metabolism</subject><subject>Virulence Factors, Bordetella - pharmacology</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFtLxDAQhYMoul5-glB8EH2INknTJo-yeAPBBxX2LWSb6TbSNjVJvfx7s-5iICQwZ87M-RA6JfkVyUl5_ZLnlGBJubgg4pKzipd4sYNmJBcMM04Wu2j2LzlAhyG85-kUkuyjfVFQmb4z9Hk7WgO-11228u4rtlmj6-g87sFYHcFkwa4G3dlhlbkmu7-wl3j0LoIdsuiypLWfOlo3rKtj60K6nR11gJAlidcR11MXJ5-cWhh1dPVPhHCM9hrdBTjZvkfo7e72df6An57vH-c3T7imlH9jQgWQysglF4ZCUcqi1FXF6xSpYaIRlZSk0EsDQhqTwkKKWlZMctpoqU3DjtD5xjft_DFBiKq3oYau0wO4KaiK84qVNE9CvhHW3oXgoVGjt732P4rkas1b_fFWa5iKCPXHWy1S3-l2wLRMyP67toBT_WxTb-2q_bIe1NK6uoVe0TK5KJa2Zb-WOYkH</recordid><startdate>19930215</startdate><enddate>19930215</enddate><creator>Yang, L</creator><creator>Camoratto, A M</creator><creator>Baffy, G</creator><creator>Raj, S</creator><creator>Manning, D R</creator><creator>Williamson, J R</creator><general>American Society for Biochemistry and Molecular Biology</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>19930215</creationdate><title>Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes</title><author>Yang, L ; Camoratto, A M ; Baffy, G ; Raj, S ; Manning, D R ; Williamson, J R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c225x-128e17d9b58d2e46946a775c925f38f879914abde89dd002e258673952fa9adf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Adenosine Diphosphate Ribose - metabolism</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Calcium - metabolism</topic><topic>Cells, Cultured</topic><topic>Diglycerides - metabolism</topic><topic>Enzyme Activation</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Inositol 1,4,5-Trisphosphate - metabolism</topic><topic>Isoenzymes - metabolism</topic><topic>Kinetics</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Molecular Sequence Data</topic><topic>Oligopeptides - chemical synthesis</topic><topic>Oligopeptides - immunology</topic><topic>Pertussis Toxin</topic><topic>Phosphorylation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Time Factors</topic><topic>Type C Phospholipases - metabolism</topic><topic>Virulence Factors, Bordetella - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, L</creatorcontrib><creatorcontrib>Camoratto, A M</creatorcontrib><creatorcontrib>Baffy, G</creatorcontrib><creatorcontrib>Raj, S</creatorcontrib><creatorcontrib>Manning, D R</creatorcontrib><creatorcontrib>Williamson, J R</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 biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, L</au><au>Camoratto, A M</au><au>Baffy, G</au><au>Raj, S</au><au>Manning, D R</au><au>Williamson, J R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1993-02-15</date><risdate>1993</risdate><volume>268</volume><issue>5</issue><spage>3739</spage><epage>3746</epage><pages>3739-3746</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Hepatocytes were established in tissue culture in order to study the effects of pertussis toxin (PT) on epidermal growth factor
(EGF)-mediated cellular responses under in vitro conditions. EGF caused a 3-fold increase of myo-inositol 1,4,5-trisphosphate
(Ins-1,4,5-P3) mass and a 50% increase of diacylglycerol mass within the first minute, with the change of diacylglycerol content
being 100-fold greater than that of Ins-1,4,5-P3. Diacylglycerol, but not Ins-1,4,5-P3, continued to accumulate over several
hours, indicating that EGF increased the hydrolysis of lipids other than phosphatidylinositol 4,5-bisphosphate (PIP2). EGF
increased phosphoinositide-specific phospholipase C-gamma (PLC-gamma) tyrosine phosphorylation within 1 min, but no effect
was observed with vasopressin, insulin, or glucagon after 5 min. EGF also caused a rapid, tyrosine kinase-dependent association
of G(i) alpha with PLC-gamma, which was maximal within 10 min. In contrast to our previous data on fresh hepatocytes, PT had
no effect on the EGF-induced tyrosine phosphorylation of PLC-gamma, although Ins-1,4,5-P3 and diacylglycerol production were
inhibited. The role of G-proteins in EGF signaling was investigated further by microinjection of G alpha antibodies into single
fura-2-loaded hepatocytes. Anti-G(i) alpha (common) antibodies prevented EGF-induced but not vasopressin-induced Ca2+ transients.
These results strengthen previous observations that a PT-sensitive G-protein is involved in EGF-mediated phospholipid metabolism
in hepatocytes and show that tyrosine phosphorylation of PLC-gamma is an insufficient signal for activation of PIP2 hydrolysis.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8429049</pmid><doi>10.1016/S0021-9258(18)53756-X</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 1993-02, Vol.268 (5), p.3739-3746 |
| issn | 0021-9258 1083-351X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenosine Diphosphate Ribose - metabolism Amino Acid Sequence Animals Antibodies Calcium - metabolism Cells, Cultured Diglycerides - metabolism Enzyme Activation Epidermal Growth Factor - pharmacology GTP-Binding Proteins - metabolism Inositol 1,4,5-Trisphosphate - metabolism Isoenzymes - metabolism Kinetics Liver - drug effects Liver - metabolism Male Molecular Sequence Data Oligopeptides - chemical synthesis Oligopeptides - immunology Pertussis Toxin Phosphorylation Rats Rats, Sprague-Dawley Signal Transduction - drug effects Time Factors Type C Phospholipases - metabolism Virulence Factors, Bordetella - pharmacology |
| title | Epidermal growth factor-mediated signaling of G(i)-protein to activation of phospholipases in rat-cultured hepatocytes |
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