Transmembrane domain-induced oligomerization is crucial for the functions of syndecan-2 and syndecan-4.
The syndecans are known to form homologous oligomers that may be important for their functions. We have therefore determined the role of oligomerization of syndecan-2 and syndecan-4. A series of glutathione S-transferase-syndecan-2 and syndecan-4 chimeric proteins showed that all syndecan constructs containing the transmembrane domain formed SDS-resistant dimers, but not those lacking it. SDS-resistant dimer formation was hardly seen in the syndecan chimeras where each transmembrane domain was substituted with that of platelet-derived growth factor receptor (PDGFR). Increased MAPK activity was detected in HEK293T cells transfected with syndecan/PDGFR chimeras in a syndecan transmembrane domain-dependent fashion. The chimera-induced MAPK activation was independent of both ligand and extracellular domain, implying that the transmembrane domain is sufficient to induce dimerization/oligomerization in vivo. Furthermore, the syndecan chimeras were defective in syndecan-4-mediated focal adhesion formation and protein kinase Calpha activation or in syndecan-2-mediated cell migration. Taken together, these data suggest that the transmembrane domains are sufficient for inducing dimerization and that transmembrane domain-induced oligomerization is crucial for syndecan-2 and syndecan-4 functions.
Choi
Sungmun
S
Department of Life Sciences, Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, Seoul 120-750, Korea.
Lee
Eunjung
E
Kwon
Soojin
S
Park
Haein
H
Yi
Jae Youn
JY
Kim
Seungin
S
Han
Inn-Oc
IO
Yun
Yungdae
Y
Oh
Eok-Soo
ES
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D017931:DNA Primers / Q000737:chemistry; D019281:Dimerization; D004789:Enzyme Activation; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000737:chemistry*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D053669:Syndecan-2; D053671:Syndecan-4; D014162:Transfection
D017931:DNA Primers; D008024:Ligands; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D011993:Recombinant Fusion Proteins; C508245:SDC2 protein, human; C508304:SDC4 protein, human; D053671:Syndecan-4; D053669:Syndecan-2; D005982:Glutathione Transferase; D017479:Receptors, Platelet-Derived Growth Factor; D051571:Protein Kinase C-alpha