ATreceptors recruit c-Src, SHP-1 and FAK upon activation by Ang II in PND15 rat hindbrain

Leonardo R Seguin1, Rodrigo S Villarreal, Gladys M Ciuffo

  • 1Instituto Multidisciplinario de Investigaciones Biológicas (IMIBIO-SL CONICET), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina.

Insights

Angiotensin II AT(2) receptors activate SHP-1, c-Src, and FAK in developing rat brains, suggesting a role in cerebellar development and neuronal differentiation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • The functional role and signaling pathways of Angiotensin II AT(2) receptors remain largely undefined.
  • AT(2) receptors are known to activate unconventional signaling pathways, often independent of classical G-protein involvement.
  • These receptors are implicated in neuronal development, including neuron migration.

Purpose of the Study:

  • To investigate the signal transduction mechanism of AT(2) receptors in the developing rat hindbrain.
  • To determine the involvement of SHP-1, c-Src, and FAK in AT(2) receptor signaling during a critical cerebellar development period.

Main Methods:

  • Co-immunoprecipitation assays were used to detect protein-protein interactions.
  • Western blotting and enzyme activity assays were employed to assess protein phosphorylation and activity.
  • Specific inhibitors (PD123319 and PP2) were used to probe signaling pathways.

Main Results:

  • Stimulation of AT(2) receptors induced transient tyrosine phosphorylation and activation of SHP-1.
  • c-Src was recruited to AT(2) receptors and mediated SHP-1 phosphorylation and activation.
  • AT(2) immunoprecipitates contained the 85kDa fragment of FAK, which associated with SHP-1.

Conclusions:

  • An active signal transduction complex involving AT(2)/SHP-1/c-Src/p85FAK exists in the PND15 rat hindbrain.
  • This signaling pathway suggests a potential role for Angiotensin II AT(2) receptors in cerebellar development and neuronal differentiation.

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