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Published on: September 9, 2021
The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver
G Hellgren1, J O Jansson, L M Carlsson
1Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Sweden.
Abstract:
Studies in cell lines have shown that Jak2 is the primary tyrosine kinase involved in signal transduction by the growth hormone receptor (GHR). In addition, growth hormone (GH) stimulates tyrosine phosphorylation of Jak1 and Jak3 in certain cell lines, while the effect on Tyk2 has not been analysed. We have investigated the expression of Jak proteins in human liver and analysed their interactions with the GHR. Using Western blot analysis and immunohistochemistry, we demonstrate that Jak1, Jak2, Jak3 and Tyk2 are present in human liver. Immunoprecipitation by an antibody against the GHR (Mab 263) followed by immunoblotting with specific antibodies against Jak proteins showed that Jak1, Jak2 and Tyk2 were associated with the GHR in this tissue. We conclude that the GHR associates with Jak1, Jak2 and Tyk2 in human liver. Although experiments in vitro indicate that Jak2 mediates GH signalling, our results open the possibility that other Jak proteins may influence GHR signalling in human liver.
Insights
Growth hormone receptor (GHR) signaling in the liver involves Janus kinases (Jak). This study found Jak1, Jak2, and Tyk2 associate with the GHR in human liver, suggesting broader signaling roles beyond Jak2.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- Janus kinases (Jak) are crucial for cytokine and growth factor signaling.
- Jak2 is identified as the primary tyrosine kinase in growth hormone receptor (GHR) signal transduction in cell line studies.
- The involvement of other Jak proteins (Jak1, Jak3, Tyk2) in GHR signaling in human liver remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and interaction of Jak proteins (Jak1, Jak2, Jak3, Tyk2) with the GHR in human liver tissue.
- To explore the potential roles of different Jak proteins in GHR signaling within the hepatic context.
Main Methods:
- Western blot analysis to detect Jak protein expression in human liver.
- Immunohistochemistry to visualize Jak protein localization in liver tissue.
- Immunoprecipitation using an anti-GHR antibody followed by immunoblotting to identify associated Jak proteins.
Main Results:
- Jak1, Jak2, Jak3, and Tyk2 proteins were detected in human liver.
- Immunoprecipitation assays revealed that Jak1, Jak2, and Tyk2 are physically associated with the GHR in human liver.
- Jak3 was detected in the liver but did not show association with the GHR under the experimental conditions.
Conclusions:
- The GHR in human liver associates with Jak1, Jak2, and Tyk2.
- While Jak2 is known to mediate GHR signaling in vitro, these findings suggest that Jak1 and Tyk2 may also play significant roles in GHR signal transduction in the human liver.
- Further research is warranted to elucidate the specific functions of these associated Jak proteins in hepatic GHR signaling pathways.
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