ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA
Authors
Thodeti, Charles KumarAlbrechtsen, Reidar
Grauslund, Morten
Asmar, Meena
Larsson, Christer
Takada, Yoshikazu
Mercurio, Arthur M.
Couchman, John R.
Wewer, Ulla M.
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2003-01-02Keywords
ADAM ProteinsAmino Acid Sequence
Animals
Antibodies, Monoclonal
Antigens, CD29
CHO Cells
Cell Adhesion
Cell Movement
Cricetinae
Cysteine
DNA, Complementary
Humans
Immunohistochemistry
Membrane Proteins
Metalloendopeptidases
Microscopy, Fluorescence
Microscopy, Phase-Contrast
Models, Biological
Molecular Sequence Data
Muscle Proteins
Protein Kinase C
Protein Kinase C-alpha
Protein Structure, Tertiary
Rats
Sequence Homology, Amino Acid
*Signal Transduction
Transfection
rhoA GTP-Binding Protein
Cancer Biology
Neoplasms
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2003 Mar 14;278(11):9576-84. Epub 2002 Dec 31. Link to article on publisher's siteDOI
10.1074/jbc.M208937200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26250PubMed ID
12509413Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M208937200
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