Cellular internalization and trafficking of 20 KDa human growth hormone.

Twenty kilodalton human growth hormone (20K-GH) is the second most abundant GH isoform after the twenty-two kilodalton human growth hormone (22 K-GH) isoform. 20K-GH exhibits similar but not identical physiological activities as that of 22K-GH. The cell behaviour of 22K-GH has been extensively studied, but little or no information has been reported regarding 20K-GH. Here, we focussed on the internalization of 20K-GH. We found that the internalization of 20K-GH is rapid and occurs in a time- and dose-dependent manner. 20K-GH internalization is mediated by GHR. It appears that the internalization of 20K-GH and GHR into the cytoplasm is mediated by clathrin and/or caveolin. The current study indicates that 20K-GH can internalize into the cytoplasm and suggests that the internalized 20K-GH may exhibit different functions from those of 22K-GH.

An extract of Perilla stem inhibits Src homology phosphatase-1 (SHP)-1 and influences insulin signaling.

Protein tyrosine phosphatases (PTPs) are enzymes that catalyze protein tyrosine dephosphorylation of which Src homology phosphatase-1 (SHP-1) is one of the best-validated, a widely distributed intracellular tyrosine phosphatase that contains two SH2 domains. Down regulation of SHP-1 tyrosine phosphatases was significantly increased sensitivity to insulin in insulin signaling pathway. Through in vitro enzymatic reaction kinetics experiment, we found that the extract of Perilla stem was a potential inhibitor to δSHP-1, the catalytic domain of SHP-1 protein tyrosine phosphatase, and its IC(50) was 4ug/ml, and was more sensitive towards SHP-1than other PTPs, which indicated that SHP-1 might be a target of the extract of Perilla stem. It can strengthened the level of tyrosine phosphorylation of insulin receptor (IR) and extracellular signal-regulated protein kinase (ERK) in HepG2 cells, and then activated the insulin signaling pathway through inhibiting the protein phosphorylation of SHP-1. These results demonstrated that the extract of Perilla stem could play an important role for diabetes treatment through inhibiting the level of SHP-1 in insulin signaling pathway.