Src mediates β-adrenergic receptor induced YAP tyrosine phosphorylation

Area of Science:

• Cell Biology
• Molecular Signaling
• Biochemistry

Background:

• The Hippo pathway is a conserved regulator of cell proliferation, with Yes-associated protein (YAP) as a key downstream effector.
• Phosphorylation critically regulates YAP activity and function.
• Beta-adrenergic receptors (β-ARs), a type of G protein-coupled receptor (GPCR), influence cell proliferation but their role in YAP regulation is unknown.

Purpose of the Study:

• To investigate the role of β-AR in regulating YAP.
• To elucidate the molecular mechanism by which β-AR affects YAP.
• To establish the signaling pathway downstream of β-AR involved in cell proliferation.

Main Methods:

• Investigated the effect of β-AR stimulation on YAP phosphorylation.
• Utilized tyrosine kinase Src inhibitors to assess its role in the β-AR signaling pathway.
• Examined the impact of inhibiting Src kinase activity on YAP phosphorylation and cell proliferation.

Main Results:

• β-AR stimulation significantly enhances YAP tyrosine phosphorylation.
• β-AR activation leads to the activation of tyrosine kinase Src.
• Src phosphorylates YAP at tyrosine residue Y357.
• Inhibition of Src kinase activity attenuates β-AR-induced YAP tyrosine phosphorylation and cell proliferation.

Conclusions:

• β-adrenergic receptors induce YAP tyrosine phosphorylation.
• The Src/YAP signaling axis is identified as a critical pathway downstream of GPCRs.
• This pathway plays a significant role in mediating β-AR-induced cell proliferation.