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Growth hormone receptor interaction with Jak proteins differs between tissues
G Hellgren1, K Albertsson-Wikland, H Billig
1Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
Abstract:
Janus kinases (Jak) play an important role in the initial steps of cytokine receptor signaling. The specificity of the four members of the Jak family (Jak1, Jak2, Jak3, and Tyk2) for different cytokine receptors is not fully understood. Recent studies have indicated that a specific cytokine receptor can activate several Jak and that this may differ between tissues. The growth hormone receptor (GHR) is believed to interact predominantly with Jak2, but studies on cell lines have shown that it may also induce phosphorylation of Jak1 and Jak3. Little is known about the interaction between the GHR and Jak in tissues. Our aim, therefore, was to elucidate which Jak interact with the GHR in two target tissues for GH, liver and adipose tissue. Western blot analysis showed that all four members of the Jak family are present in both rat liver and adipose tissue. However, coprecipitation using an anti-GHR antibody revealed that only Jak1 and Jak2 were associated with the GHR in these tissues. The relative amount of Jak1 and Jak2 that coprecipitated with the GHR differed markedly between tissues. In the liver, Jak2 dominated, and only a small amount of Jak1 was detected. In adipose tissue, at least one third of the coprecipitated Jak was Jak1. This is the first study to show that both Jak1 and Jak2 are associated with the GHR in rat tissues. The difference in the ratio between GHR-associated Jak1 and Jak2 in liver and adipose tissue may indicate that GHR signaling in different tissues could differ in terms of Jak specificity.
Insights
This study reveals that Janus kinases (Jak) 1 and Jak2 associate with the growth hormone receptor (GHR) in rat liver and adipose tissues, with distinct ratios indicating tissue-specific signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Endocrinology
Background:
- Janus kinases (Jak) are crucial for cytokine receptor signaling, but their specific interactions with receptors like the growth hormone receptor (GHR) in different tissues remain unclear.
- While cell line studies suggest GHR interacts with Jak1, Jak2, and Jak3, in vivo data, particularly in target tissues, is limited.
Purpose of the Study:
- To investigate the specific Janus kinase (Jak) members that interact with the growth hormone receptor (GHR) in rat liver and adipose tissue.
- To determine if the Jak-GHR association differs between these two key growth hormone target tissues.
Main Methods:
- Western blot analysis was employed to detect the presence of all four Jak family members (Jak1, Jak2, Jak3, Tyk2) in rat liver and adipose tissue extracts.
- Coprecipitation assays using an anti-GHR antibody were performed to identify which Jak members physically associate with the GHR in these tissues.
Main Results:
- All four Jak family members were found in both liver and adipose tissue.
- Coprecipitation confirmed that only Jak1 and Jak2 associate with the GHR in these tissues.
- A significant difference in the Jak1:Jak2 ratio associated with GHR was observed between tissues: Jak2 predominated in the liver, while Jak1 constituted at least one-third of the associated Jak in adipose tissue.
Conclusions:
- This is the first study demonstrating the association of both Jak1 and Jak2 with the GHR in rat tissues.
- The distinct ratios of GHR-associated Jak1 and Jak2 in liver versus adipose tissue suggest that GHR signaling specificity may vary between tissues.