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Growth hormone signal transduction
Graciela Piwien-Pilipuk1, Jeffrey S Huo, Jessica Schwartz
1Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Abstract:
Multiple signaling pathways mediate the diverse effects of growth hormone (GH) on growth and metabolism. The interaction of GH with GH receptors (GHR) on target cells promotes the association of the cellular tyrosine kinase JAK2 with the GHR, initiating tyrosine phosphorylation of GHR and JAK2, and activation of multiple signaling cascades. GH-stimulated activation of signal transducers and activators of transcription (STATs), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3' kinase (PI3K) cascades have been shown to regulate the transcription of GH-responsive genes. Cross-talk among these signaling cascades in regulating specific genes suggests that GH signaling to the nucleus involves a GH-regulated signaling network.
Insights
Growth hormone (GH) triggers cell signaling pathways by binding to its receptor, activating JAK2 kinase. This initiates complex networks regulating gene transcription for growth and metabolism.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Signaling
Background:
- Growth hormone (GH) exerts varied effects on growth and metabolism through multiple signaling pathways.
- GH initiates intracellular signaling upon binding to the GH receptor (GHR) on target cells.
Purpose of the Study:
- To elucidate the intricate signaling network downstream of GH receptor activation.
- To understand how GH signaling cascades regulate gene transcription.
Main Methods:
- Investigated the interaction between GH and GHR.
- Analyzed the activation of JAK2 tyrosine kinase.
- Examined the downstream signaling pathways including STATs, MAPK, and PI3K.
Main Results:
- GH binding to GHR leads to JAK2 association and tyrosine phosphorylation.
- Activation of STAT, MAPK, and PI3K signaling cascades was observed.
- Evidence suggests cross-talk among these pathways in regulating GH-responsive genes.
Conclusions:
- GH signaling involves a complex network of interconnected pathways.
- This network integrates signals to regulate gene transcription and mediate GH's effects.