Regulation of ErbB4 via stimulation of GPCR for neurotransmitter and synaptic functions

ErbB 4属于ErbB蛋白家族，在神经元中大量表达。它在突触功能中起重要作用。在前期的工作中，我们发现促性腺激素释放激素（GnRH）在下丘脑神经元（GT 1 -7细胞）中反式激活ErbB 4。我们还发现，较高浓度的GnRH诱导ErbB 4的切割。在本研究中，我们研究了GnRH诱导的ErbB 4激活和切割的分子机制。通过ErbB 4诱导的ERK激活来测量ErbB 4激活。我们发现Gq/11蛋白、PKC、PKD、Fyn和PYK 2参与了ErbB 4的激活。与此相反，只有Gq/11蛋白和PKC，而不是PKD，Fyn和PYK 2，参与ErbB 4的切割。这些结果表明，PKC激活后ErbB 4的激活和裂解是通过不同的分子机制诱导的。

ErbB4 belongs to the ErbB protein family and is abundantly expressed in neurons. It plays important roles in synaptic functions. In the previous work, we found that gonadotropin-releasing hormone (GnRH) transactivated ErbB4 in hypothalamic neurons (GT1-7 cells). We also found that the higher concentration of GnRH induced the cleavage of ErbB4. In the present study, we examined the molecular mechanisms of GnRH-induced activation and cleavage of ErbB4. ErbB4 activation was measured by the ErbB4-induced activation of ERK. We found that Gq/11 proteins, PKC, PKD, Fyn and PYK2 were involved in the activation of ErbB4. In contrast, only Gq/11 proteins and PKC, but not PKD, Fyn and PYK2, were involved in the cleavage of ErbB4. These results suggest that the activation and cleavage of ErbB4 are induced by different molecular mechanisms after PKC activation.