Seasholtz A F, Gamm D M, Ballestero R P, Scarpetta M A, Uhler M D
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109.
Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1734-8. doi: 10.1073/pnas.92.5.1734.
Many neurotransmitters are known to regulate neuronal cell function by means of activation of cAMP-dependent protein kinase (PKA) and phosphorylation of neuronal substrate proteins, including transcription factors and ion channels. Here, we have characterized the gene expression of two isoforms of a protein kinase inhibitor (PKI) specific for PKA in mouse brain by RNase protection and in situ hybridization histochemistry. The studies demonstrate that the PKI alpha isoform is abundant in many regions of the adult mouse brain but particularly in cerebellum, hypothalamus, hippocampus, and cortex. In contrast, PKI beta is present at much lower levels in most brain regions but is found in significant amounts in the cerebellum, as well as in distinct nuclei within the pons, medulla, and hypothalamus. These results are consistent with a regulatory role of endogenous PKI in PKA-mediated signal transduction in brain and suggest differential functions for the two isoforms of PKI within the central nervous system.
已知许多神经递质通过激活环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）和使包括转录因子和离子通道在内的神经元底物蛋白磷酸化来调节神经元细胞功能。在此，我们通过核糖核酸酶保护和原位杂交组织化学对小鼠脑中对PKA具有特异性的蛋白激酶抑制剂（PKI）的两种同工型的基因表达进行了表征。研究表明，PKIα同工型在成年小鼠脑的许多区域中含量丰富，但在小脑、下丘脑、海马体和皮质中尤为明显。相比之下，PKIβ在大多数脑区中的含量要低得多，但在小脑中以及脑桥、延髓和下丘脑的不同核团中含量显著。这些结果与内源性PKI在脑中PKA介导的信号转导中的调节作用一致，并表明PKI的两种同工型在中枢神经系统中具有不同的功能。
