Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence
Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differenti...
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| Veröffentlicht in: | The EMBO journal 1999-06, Vol.18 (11), p.3013-3023 |
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| creator | Chiaradonna, F Fontana, L Iavarone, C Carriero, M V Scholz, G Barone, M V Stoppelli, M P |
| description | Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo. |
| doi_str_mv | 10.1093/emboj/18.11.3013 |
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Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1093/emboj/18.11.3013</identifier><identifier>PMID: 10357814</identifier><language>eng</language><publisher>England</publisher><subject>Actins - metabolism ; Animals ; Calcitriol - pharmacology ; Cell Adhesion - drug effects ; Cell Differentiation ; Cell Movement - drug effects ; Cytoskeleton - drug effects ; Enzyme Activation ; Humans ; Macrophages - cytology ; Macrophages - drug effects ; Macrophages - enzymology ; Macrophages - metabolism ; Mice ; Monocytes - cytology ; Monocytes - drug effects ; Monocytes - enzymology ; Monocytes - metabolism ; Mutation ; Phenotype ; Phosphorylation - drug effects ; Protein Kinase Inhibitors ; Protein Kinases - metabolism ; Protein-Tyrosine Kinases - genetics ; Protein-Tyrosine Kinases - metabolism ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-hck ; Receptors, Cell Surface - metabolism ; Receptors, Urokinase Plasminogen Activator ; Temperature ; Transfection ; Transforming Growth Factor beta - pharmacology ; Tumor Cells, Cultured ; Urokinase-Type Plasminogen Activator - metabolism ; Urokinase-Type Plasminogen Activator - pharmacology</subject><ispartof>The EMBO journal, 1999-06, Vol.18 (11), p.3013-3023</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171383/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171383/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10357814$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chiaradonna, F</creatorcontrib><creatorcontrib>Fontana, L</creatorcontrib><creatorcontrib>Iavarone, C</creatorcontrib><creatorcontrib>Carriero, M V</creatorcontrib><creatorcontrib>Scholz, G</creatorcontrib><creatorcontrib>Barone, M V</creatorcontrib><creatorcontrib>Stoppelli, M P</creatorcontrib><title>Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><description>Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.</description><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Calcitriol - pharmacology</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Differentiation</subject><subject>Cell Movement - drug effects</subject><subject>Cytoskeleton - drug effects</subject><subject>Enzyme Activation</subject><subject>Humans</subject><subject>Macrophages - cytology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - enzymology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Monocytes - cytology</subject><subject>Monocytes - drug effects</subject><subject>Monocytes - enzymology</subject><subject>Monocytes - metabolism</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Kinase Inhibitors</subject><subject>Protein Kinases - metabolism</subject><subject>Protein-Tyrosine Kinases - genetics</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-hck</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Urokinase Plasminogen Activator</subject><subject>Temperature</subject><subject>Transfection</subject><subject>Transforming Growth Factor beta - pharmacology</subject><subject>Tumor Cells, Cultured</subject><subject>Urokinase-Type Plasminogen Activator - metabolism</subject><subject>Urokinase-Type Plasminogen Activator - pharmacology</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1r3DAQxUVpSTYf956KTqU5eFdj2ZZ0KZTQJoFAL8nZjOVxV4ktuZI2Yf-O_MPZfPXjNMy8x_vxGMY-gliCMHJFUxduVqCXAEspQL5jC6gaUZRC1e_ZQpQNFBVos88OUroRQtRawR7bByFrpaFasIfrGG6dx0Q8kqU5h1j0NJPvyWeOvueF838Pc92savNlbW9PONrs7jC74HnKmIm7xJFPYSS7GTHydO-yXfOO8j2R59OWxjAFH-w2O8stjePOnN3o8vYZhP2aInlLR-zDgGOi49d5yK5_fL86PS8uf55dnH67LOayKXMxaK3lQCCVqYyxNGjZqAZRligkdENDHQ0GjLY1PK1CUz0QaqMIVaWEPGRfX3LnTTdRb3cFI47tHN2EcdsGdO3_infr9le4awEUSC13AZ9fA2L4vaGU28mlp2LoKWxS2xgtVKnUzvjpX9IfxNsf5CPWg4-A</recordid><startdate>19990601</startdate><enddate>19990601</enddate><creator>Chiaradonna, F</creator><creator>Fontana, L</creator><creator>Iavarone, C</creator><creator>Carriero, M V</creator><creator>Scholz, G</creator><creator>Barone, M V</creator><creator>Stoppelli, M P</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19990601</creationdate><title>Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence</title><author>Chiaradonna, F ; Fontana, L ; Iavarone, C ; Carriero, M V ; Scholz, G ; Barone, M V ; Stoppelli, M P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p262t-f8883fe1379499cef83676aa32a031bf6ebef9198c511bf608e5fea897ea74703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Calcitriol - pharmacology</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Differentiation</topic><topic>Cell Movement - drug effects</topic><topic>Cytoskeleton - drug effects</topic><topic>Enzyme Activation</topic><topic>Humans</topic><topic>Macrophages - cytology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - enzymology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Monocytes - cytology</topic><topic>Monocytes - drug effects</topic><topic>Monocytes - enzymology</topic><topic>Monocytes - metabolism</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Kinase Inhibitors</topic><topic>Protein Kinases - metabolism</topic><topic>Protein-Tyrosine Kinases - genetics</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-hck</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Urokinase Plasminogen Activator</topic><topic>Temperature</topic><topic>Transfection</topic><topic>Transforming Growth Factor beta - pharmacology</topic><topic>Tumor Cells, Cultured</topic><topic>Urokinase-Type Plasminogen Activator - metabolism</topic><topic>Urokinase-Type Plasminogen Activator - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chiaradonna, F</creatorcontrib><creatorcontrib>Fontana, L</creatorcontrib><creatorcontrib>Iavarone, C</creatorcontrib><creatorcontrib>Carriero, M V</creatorcontrib><creatorcontrib>Scholz, G</creatorcontrib><creatorcontrib>Barone, M V</creatorcontrib><creatorcontrib>Stoppelli, M P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chiaradonna, F</au><au>Fontana, L</au><au>Iavarone, C</au><au>Carriero, M V</au><au>Scholz, G</au><au>Barone, M V</au><au>Stoppelli, M P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence</atitle><jtitle>The EMBO journal</jtitle><addtitle>EMBO J</addtitle><date>1999-06-01</date><risdate>1999</risdate><volume>18</volume><issue>11</issue><spage>3013</spage><epage>3023</epage><pages>3013-3023</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><abstract>Anchorage-independent myelomonocytic cells acquire adherence within minutes of differentiation stimuli, such as the proteolytically inactive N-terminal fragment of urokinase binding to its cognate glycosylphosphatidylinositol (GPI)-anchored receptor. Here, we report that urokinase-treated differentiating U937 monocyte-like cells exhibit a rapid and transient inhibition of p56/59(hck) and p55(fgr) whereas no changes in the activity of other Src family kinases, such as p53/56(lyn) and p59(fyn) were observed. U937 transfectants expressing a kinase-defective (Lys267 to Met) p56/59(hck) variant exhibit enhanced adhesiveness and a marked F-actin redistribution in thin protruding structures. Conversely, urokinase as well as expression of wild-type or constitutively active (Tyr499 to Phe) p56/59(hck) stimulates the directional migration of uninduced U937 cells. Accordingly, expression of constitutively active or kinase inactive p56/59(hck) selectively prevents urokinase receptor-dependent induction of either adhesion or motility, indicating that a specific activation state of p56/59(hck) is required for each cell response. In conclusion, modulation of the intracellular p56/59(hck) tyrosine kinase activity switches cell motility towards adherence, providing a mutually exclusive mechanism to regulate these properties during monocyte/macrophage differentiation in vivo.</abstract><cop>England</cop><pmid>10357814</pmid><doi>10.1093/emboj/18.11.3013</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Online Library Free Content; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Actins - metabolism Animals Calcitriol - pharmacology Cell Adhesion - drug effects Cell Differentiation Cell Movement - drug effects Cytoskeleton - drug effects Enzyme Activation Humans Macrophages - cytology Macrophages - drug effects Macrophages - enzymology Macrophages - metabolism Mice Monocytes - cytology Monocytes - drug effects Monocytes - enzymology Monocytes - metabolism Mutation Phenotype Phosphorylation - drug effects Protein Kinase Inhibitors Protein Kinases - metabolism Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-hck Receptors, Cell Surface - metabolism Receptors, Urokinase Plasminogen Activator Temperature Transfection Transforming Growth Factor beta - pharmacology Tumor Cells, Cultured Urokinase-Type Plasminogen Activator - metabolism Urokinase-Type Plasminogen Activator - pharmacology |
| title | Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence |
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