Show simple item record

dc.contributor.authorThodeti, Charles Kumar
dc.contributor.authorAlbrechtsen, Reidar
dc.contributor.authorGrauslund, Morten
dc.contributor.authorAsmar, Meena
dc.contributor.authorLarsson, Christer
dc.contributor.authorTakada, Yoshikazu
dc.contributor.authorMercurio, Arthur M.
dc.contributor.authorCouchman, John R.
dc.contributor.authorWewer, Ulla M.
dc.date2022-08-11T08:08:01.000
dc.date.accessioned2022-08-23T15:39:46Z
dc.date.available2022-08-23T15:39:46Z
dc.date.issued2003-01-02
dc.date.submitted2010-11-07
dc.identifier.citationJ Biol Chem. 2003 Mar 14;278(11):9576-84. Epub 2002 Dec 31. <a href="http://dx.doi.org/10.1074/jbc.M208937200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M208937200
dc.identifier.pmid12509413
dc.identifier.urihttp://hdl.handle.net/20.500.14038/26250
dc.description.abstractThe ADAMs (a disintegrin and metalloprotease) comprise a large family of multidomain proteins with cell-binding and metalloprotease activities. The ADAM12 cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation. This process contrasts with cell adhesion on fibronectin, which is integrin-initiated but syndecan-4-dependent. In the present study, we investigated ADAM12/syndecan-4 signaling leading to cell spreading and stress fiber formation. We demonstrate that syndecan-4, when present in significant amounts, promotes beta(1) integrin-dependent cell spreading and stress fiber formation in response to rADAM12-cys. A mutant form of syndecan-4 deficient in protein kinase C (PKC)alpha activation or a different member of the syndecan family, syndecan-2, was unable to promote cell spreading. GF109203X and Go6976, inhibitors of PKC, completely inhibited ADAM12/syndecan-4-induced cell spreading. Expression of syndecan-4, but not syn4DeltaI, resulted in the accumulation of activated beta(1) integrins at the cell periphery in Chinese hamster ovary beta1 cells as revealed by 12G10 staining. Further, expression of myristoylated, constitutively active PKCalpha resulted in beta(1) integrin-dependent cell spreading, but additional activation of RhoA was required to induce stress fiber formation. In summary, these data provide novel insights into syndecan-4 signaling. Syndecan-4 can promote cell spreading in a beta(1) integrin-dependent fashion through PKCalpha and RhoA, and PKCalpha and RhoA likely function in separate pathways.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12509413&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M208937200
dc.subjectADAM Proteins
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectAntibodies, Monoclonal
dc.subjectAntigens, CD29
dc.subjectCHO Cells
dc.subjectCell Adhesion
dc.subjectCell Movement
dc.subjectCricetinae
dc.subjectCysteine
dc.subjectDNA, Complementary
dc.subjectHumans
dc.subjectImmunohistochemistry
dc.subjectMembrane Proteins
dc.subjectMetalloendopeptidases
dc.subjectMicroscopy, Fluorescence
dc.subjectMicroscopy, Phase-Contrast
dc.subjectModels, Biological
dc.subjectMolecular Sequence Data
dc.subjectMuscle Proteins
dc.subjectProtein Kinase C
dc.subjectProtein Kinase C-alpha
dc.subjectProtein Structure, Tertiary
dc.subjectRats
dc.subjectSequence Homology, Amino Acid
dc.subject*Signal Transduction
dc.subjectTransfection
dc.subjectrhoA GTP-Binding Protein
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.titleADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume278
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/cancerbiology_pp/164
dc.identifier.contextkey1633389
html.description.abstract<p>The ADAMs (a disintegrin and metalloprotease) comprise a large family of multidomain proteins with cell-binding and metalloprotease activities. The ADAM12 cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta(1) integrin-dependent cell spreading, stress fiber assembly, and focal adhesion formation. This process contrasts with cell adhesion on fibronectin, which is integrin-initiated but syndecan-4-dependent. In the present study, we investigated ADAM12/syndecan-4 signaling leading to cell spreading and stress fiber formation. We demonstrate that syndecan-4, when present in significant amounts, promotes beta(1) integrin-dependent cell spreading and stress fiber formation in response to rADAM12-cys. A mutant form of syndecan-4 deficient in protein kinase C (PKC)alpha activation or a different member of the syndecan family, syndecan-2, was unable to promote cell spreading. GF109203X and Go6976, inhibitors of PKC, completely inhibited ADAM12/syndecan-4-induced cell spreading. Expression of syndecan-4, but not syn4DeltaI, resulted in the accumulation of activated beta(1) integrins at the cell periphery in Chinese hamster ovary beta1 cells as revealed by 12G10 staining. Further, expression of myristoylated, constitutively active PKCalpha resulted in beta(1) integrin-dependent cell spreading, but additional activation of RhoA was required to induce stress fiber formation. In summary, these data provide novel insights into syndecan-4 signaling. Syndecan-4 can promote cell spreading in a beta(1) integrin-dependent fashion through PKCalpha and RhoA, and PKCalpha and RhoA likely function in separate pathways.</p>
dc.identifier.submissionpathcancerbiology_pp/164
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages9576-84


This item appears in the following Collection(s)

Show simple item record