Multimerization of the cytoplasmic domain of syndecan-4 is required for its ability to activate protein kinase C.

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E S Oh, A Woods, J R Couchman

The transmembrane proteoglycan syndecan-4, which is a coreceptor with integrins in cytoskeleton-matrix interactions, appears to be multimerized in vivo. Both purified and recombinant core proteins form sodium dodecyl sulfate-resistant oligomers, and we now report that a synthetic peptide corresponding to the central region of syndecan-4 cytoplasmic domain (4V) also oligomerizes. The degree of oligomerization correlates with the previously reported ability to bind protein kinase C (PKC) and regulate its activity. Only multimeric recombinant syndecan-4 core protein, but not the monomeric protein, potentiated the activity of PKCalpha, and only oligomeric syndecan-4 cytoplasmic peptides were active. Changes in peptide sequence caused parallel loss of stable oligomeric status and ability to regulate a mixture of PKCalphabetagamma activity. A synthetic peptide encompassing the whole cytoplasmic domain of syndecan-4 (4L) containing a membrane-proximal basic sequence did not form higher order oligomers and could not regulate the activity of PKCalphabetagamma unless induced to aggregate by phosphatidylinositol 4,5-bisphosphate. Oligomerization and PKC regulatory activity of the 4V peptide were both increased by addition of N-terminal cysteine and reduced by phosphorylation of the cysteine thiol group. Concentration of syndecan-4 at sites of focal adhesion formation may enhance multimerization and both localize PKC and potentiate its activity to induce stable complex formation.
Original languageEnglish
JournalJournal of Biological Chemistry
Volume272
Issue number18
Pages (from-to)11805-11
Number of pages6
ISSN0021-9258
Publication statusPublished - 1997

Bibliographical note

Keywords: Adenosine Triphosphate; Amino Acid Sequence; Animals; Brain; Chromatography, Gel; Cloning, Molecular; Cytoplasm; Enzyme Activation; Isoenzymes; Kinetics; Macromolecular Substances; Membrane Glycoproteins; Molecular Sequence Data; Peptide Fragments; Protein Hybridization; Protein Kinase C; Protein Kinase C-alpha; Proteoglycans; Rabbits; Recombinant Fusion Proteins; Recombinant Proteins; Structure-Activity Relationship; Syndecan-4

ID: 5164692