Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells
Thrombin stimulates both DNA synthesis and cell morphological changes in Swiss 3T3 cells, although the mechanism of signal coordination leading to these responses is unknown. We report here that nitric oxide (NO) donors selectively enhance thrombin-stimulated p70(S6k) activity by 40-60%, an effect t...
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| Veröffentlicht in: | Biochemical and biophysical research communications 1999-12, Vol.266 (2), p.352 |
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| creator | Berven, L A Frew, I J Crouch, M F |
| description | Thrombin stimulates both DNA synthesis and cell morphological changes in Swiss 3T3 cells, although the mechanism of signal coordination leading to these responses is unknown. We report here that nitric oxide (NO) donors selectively enhance thrombin-stimulated p70(S6k) activity by 40-60%, an effect that was sustained for 24 h. Potentiation of p70(S6k) also was observed with cGMP analogues indicating that this effect is mediated by cGMP-activated protein kinase. NO donors also induced morphological changes characterized by spindle-shaped cells in confluent, nondividing cells or by extended protrusions from the trailing edge in subconfluent, polarized cells. NO donors had no significant effects on intracellular Ca(2+) mobilization, DNA synthesis, proliferation, or ERKs 1 and 2 and p90RSK activities, indicating that mitogenic responses and cell division are not altered by NO donors. We conclude that NO donors modulate the morphological changes associated with cellular motility in response to thrombin stimulation through selective enhancement of p70(S6k) activity. |
| doi_str_mv | 10.1006/bbrc.1999.1833 |
| format | Article |
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We report here that nitric oxide (NO) donors selectively enhance thrombin-stimulated p70(S6k) activity by 40-60%, an effect that was sustained for 24 h. Potentiation of p70(S6k) also was observed with cGMP analogues indicating that this effect is mediated by cGMP-activated protein kinase. NO donors also induced morphological changes characterized by spindle-shaped cells in confluent, nondividing cells or by extended protrusions from the trailing edge in subconfluent, polarized cells. NO donors had no significant effects on intracellular Ca(2+) mobilization, DNA synthesis, proliferation, or ERKs 1 and 2 and p90RSK activities, indicating that mitogenic responses and cell division are not altered by NO donors. We conclude that NO donors modulate the morphological changes associated with cellular motility in response to thrombin stimulation through selective enhancement of p70(S6k) activity.</description><identifier>ISSN: 0006-291X</identifier><identifier>DOI: 10.1006/bbrc.1999.1833</identifier><identifier>PMID: 10600507</identifier><language>eng</language><publisher>United States</publisher><subject>3T3 Cells ; Animals ; Calcium Signaling ; Cell Movement - drug effects ; Cell Size - drug effects ; Cyclic GMP-Dependent Protein Kinases - metabolism ; Enzyme Activation - drug effects ; Mice ; Microscopy, Fluorescence ; Microscopy, Phase-Contrast ; Molsidomine - pharmacology ; Nitric Oxide - pharmacology ; Nitroprusside - pharmacology ; Phalloidine ; Ribosomal Protein S6 Kinases - metabolism ; Thrombin - pharmacology ; Vasodilator Agents - pharmacology</subject><ispartof>Biochemical and biophysical research communications, 1999-12, Vol.266 (2), p.352</ispartof><rights>Copyright 1999 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10600507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berven, L A</creatorcontrib><creatorcontrib>Frew, I J</creatorcontrib><creatorcontrib>Crouch, M F</creatorcontrib><title>Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Thrombin stimulates both DNA synthesis and cell morphological changes in Swiss 3T3 cells, although the mechanism of signal coordination leading to these responses is unknown. We report here that nitric oxide (NO) donors selectively enhance thrombin-stimulated p70(S6k) activity by 40-60%, an effect that was sustained for 24 h. Potentiation of p70(S6k) also was observed with cGMP analogues indicating that this effect is mediated by cGMP-activated protein kinase. NO donors also induced morphological changes characterized by spindle-shaped cells in confluent, nondividing cells or by extended protrusions from the trailing edge in subconfluent, polarized cells. NO donors had no significant effects on intracellular Ca(2+) mobilization, DNA synthesis, proliferation, or ERKs 1 and 2 and p90RSK activities, indicating that mitogenic responses and cell division are not altered by NO donors. We conclude that NO donors modulate the morphological changes associated with cellular motility in response to thrombin stimulation through selective enhancement of p70(S6k) activity.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Calcium Signaling</subject><subject>Cell Movement - drug effects</subject><subject>Cell Size - drug effects</subject><subject>Cyclic GMP-Dependent Protein Kinases - metabolism</subject><subject>Enzyme Activation - drug effects</subject><subject>Mice</subject><subject>Microscopy, Fluorescence</subject><subject>Microscopy, Phase-Contrast</subject><subject>Molsidomine - pharmacology</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Phalloidine</subject><subject>Ribosomal Protein S6 Kinases - metabolism</subject><subject>Thrombin - pharmacology</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0006-291X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kL9PAjEcxTtoBNHV0XTU4fDbluvR0RBRE6IDDG6kP6Hau17aojL4v4tRp5d88j5veAhdEBgTAH6jVNJjIoQYkyljR2gIB1pRQV4G6DTnVwBCJlycoAEBDlBDM0RfT74kr3H89MZiE7uYMs42WF38uw173Mdiu-JlsbhsU2yV76pcfLsLB2Rw38DVkr9dY_kj-LLHsjO4janfxhA3XsuA9VZ2G5ux7_Dyw-eM2YphbUPIZ-jYyZDt-V-O0HJ-t5o9VIvn-8fZ7aLqKTSlcopOrBMaCNXOuikjpjaONKzmnBKupLRWAqcNASpAasPr2hwKbupqo9gIXf6u9jvVWrPuk29l2q__X2DfpjhgMg</recordid><startdate>19991220</startdate><enddate>19991220</enddate><creator>Berven, L A</creator><creator>Frew, I J</creator><creator>Crouch, M F</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19991220</creationdate><title>Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells</title><author>Berven, L A ; Frew, I J ; Crouch, M F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p207t-fb24ef9c012cfef831d5df173566216baaeea062710290acd655ddf1f8f5db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>3T3 Cells</topic><topic>Animals</topic><topic>Calcium Signaling</topic><topic>Cell Movement - drug effects</topic><topic>Cell Size - drug effects</topic><topic>Cyclic GMP-Dependent Protein Kinases - metabolism</topic><topic>Enzyme Activation - drug effects</topic><topic>Mice</topic><topic>Microscopy, Fluorescence</topic><topic>Microscopy, Phase-Contrast</topic><topic>Molsidomine - pharmacology</topic><topic>Nitric Oxide - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Phalloidine</topic><topic>Ribosomal Protein S6 Kinases - metabolism</topic><topic>Thrombin - pharmacology</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berven, L A</creatorcontrib><creatorcontrib>Frew, I J</creatorcontrib><creatorcontrib>Crouch, M F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berven, L A</au><au>Frew, I J</au><au>Crouch, M F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>1999-12-20</date><risdate>1999</risdate><volume>266</volume><issue>2</issue><spage>352</spage><pages>352-</pages><issn>0006-291X</issn><abstract>Thrombin stimulates both DNA synthesis and cell morphological changes in Swiss 3T3 cells, although the mechanism of signal coordination leading to these responses is unknown. We report here that nitric oxide (NO) donors selectively enhance thrombin-stimulated p70(S6k) activity by 40-60%, an effect that was sustained for 24 h. Potentiation of p70(S6k) also was observed with cGMP analogues indicating that this effect is mediated by cGMP-activated protein kinase. NO donors also induced morphological changes characterized by spindle-shaped cells in confluent, nondividing cells or by extended protrusions from the trailing edge in subconfluent, polarized cells. NO donors had no significant effects on intracellular Ca(2+) mobilization, DNA synthesis, proliferation, or ERKs 1 and 2 and p90RSK activities, indicating that mitogenic responses and cell division are not altered by NO donors. We conclude that NO donors modulate the morphological changes associated with cellular motility in response to thrombin stimulation through selective enhancement of p70(S6k) activity.</abstract><cop>United States</cop><pmid>10600507</pmid><doi>10.1006/bbrc.1999.1833</doi></addata></record> |
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| ispartof | Biochemical and biophysical research communications, 1999-12, Vol.266 (2), p.352 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 3T3 Cells Animals Calcium Signaling Cell Movement - drug effects Cell Size - drug effects Cyclic GMP-Dependent Protein Kinases - metabolism Enzyme Activation - drug effects Mice Microscopy, Fluorescence Microscopy, Phase-Contrast Molsidomine - pharmacology Nitric Oxide - pharmacology Nitroprusside - pharmacology Phalloidine Ribosomal Protein S6 Kinases - metabolism Thrombin - pharmacology Vasodilator Agents - pharmacology |
| title | Nitric oxide donors selectively potentiate thrombin-stimulated p70(S6k) activity and morphological changes in Swiss 3T3 cells |
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