APPL2 is a close homolog of APPL1 abundantly expressed in skeletal muscle. These two adaptor proteins share 52% identity and 72% similarity in amino acid sequence, and the same domain organization. APPL1 and APPL2 appear to play a similar role in mediating growth factors-induced cell proliferation in fibroblast cells and apoptosis in zebrafish. On the other hand, a recent in vitro study demonstrated that these two proteins possess distinct or even opposite functions in regulating glucose and lipid metabolism. Structural analysis revealed that APPL2 incorporates two homodimers, whereas APPL1 incorporates only one homodimer in the asymmetric unit. While APPL1 binds to the adiponectin receptors and increases adiponectin-induced glucose uptake and fatty acid oxidation, APPL2 inhibits the adiponectin actions in muscle cells. Although the insulin-sensitizing effects of APPL1 are well characterized, little is known about the physiological role of its homolog APPL2 in insulin signaling and glucose metabolism.
Relevant recent publications:
1. Signaling mechanisms underlying the insulin-sensitizing effects of adiponectin. Cheng KK, Lam KS, Wang B, Xu A. Best Pract Res Clin Endocrinol Metab. 2014 28(1):3-13
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