title: Multimerization of the cytoplasmic domain of syndecan-4 is required for its ability to activate protein kinase C.
abstract: 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.
authors.affiliation: Department of Cell Biology and the Cell Adhesion and Matrix Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Oh
authors.forename: A
authors.initials: A
authors.lastname: Woods
authors.forename: J R
authors.initials: JR
authors.lastname: Couchman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D055503:Protein Multimerization; D011509:Proteoglycans / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D053671:Syndecan-4
chemical_list: D007527:Isoenzymes; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D053671:Syndecan-4; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha