MULTIMERIZATION OF THE CYTOPLASMIC DOMAIN OF SYNDECAN-4 IS REQUIRED FOR ITS ABILITY TO ACTIVATE PROTEIN-KINASE-C

The transmembrane proteoglycan syndecan-4, which is a coreceptor with integrins in cytoskeleton-matrix interactions, appears to be multimeri zed in vivo. Both purified and recombinant core proteins form sodium d odecyl 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 correlat es with the previously reported ability to bind protein kinase C (PKC) and regulate its activity. Only multimeric recombinant syndecan-4 cor e protein, but not the monomeric protein, potentiated the activity of PKC alpha, and only oligomeric syndecan-4 cytoplasmic peptides were ac tive. Changes in peptide sequence caused parallel loss of stable oligo meric status and ability to regulate a mixture of PKC alpha beta gamma activity. A synthetic peptide encompassing the whole cytoplasmic doma in of syndecan-4 (4L) containing a membrane-proximal basic sequence di d not form higher order oligomers and could not regulate the activity of PKC alpha beta gamma unless induced to aggregate by phosphatidylino sitol 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. Concentra tion of syndecan-4 at sites of focal adhesion formation may enhance mu ltimerization and both localize PKC and potentiate its activity to ind uce stable complex formation.