Differential dimerization and association among resistin family proteins with implications for functional specificity.
Secreted by white adipose tissue as a hormone, resistin was identified as a possible link between obesity and insulin resistance. High circulating resistin levels were observed to correlate with obesity. Administration of resistin lowered the glucose tolerance threshold and impaired insulin activity; whereas anti-resistin antibodies had the opposite effects. However, contradictory data were subsequently reported in regard to the correlation between resistin expression level and obesity or type 2 diabetes. Two additional proteins that share a highly homologous C-terminus with resistin have been identified in mouse, and one in human, forming a resistin-related protein family. Resistin was shown to dimerize through a disulfide bond formed by the N-terminal-most cysteine (Cys26). Here we demonstrate that while Cys26 is both necessary and sufficient for homodimer formation, all three resistin family members can also interact with one another regardless of the presence of Cys26 through non-covalent interactions. Furthermore, protein crosslinking analysis indicated that resistin and resistin beta, but not resistin alpha, exist as multimers, probably with a dimer as the subunit. The multiple protein complex formation is obviously at a level higher than the Cys26 disulfide bonding. These results suggest the potential importance of considering intermolecular interactions among resistin family members in studying their functions.
Chen
J
J
Allele Biotechnology & Pharmaceuticals Incorporated, 6827 Nancy Ridge Drive, San Diego, California 92121, USA.
Wang
L
L
Boeg
Y S
YS
Xia
B
B
Wang
J
J
D000818:Animals; D002478:Cells, Cultured; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004220:Disulfides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000235:genetics; D006729:Hormones, Ectopic / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor; D011506:Proteins; D052243:Resistin
D004220:Disulfides; D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D020932:Nerve Growth Factor; D003545:Cysteine