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大鼠脑发育过程中微管相关蛋白MAP1B磷酸化的异质性。

Heterogeneity in the phosphorylation of microtubule-associated protein MAP1B during rat brain development.

作者信息

Ulloa L, Avila J, Díaz-Nido J

机构信息

Centro de Biología Molecular Severo Ochoa, Universidad Autónoma, Madrid, Spain.

出版信息

J Neurochem. 1993 Sep;61(3):961-72. doi: 10.1111/j.1471-4159.1993.tb03609.x.

DOI:10.1111/j.1471-4159.1993.tb03609.x
PMID:7689645
Abstract

The patterns of isoforms and of immunoreactivity of the microtubule-associated protein MAP1B toward a panel of antibodies to phosphorylation-sensitive epitopes are different in distinct rat brain regions and change during development. This suggests the occurrence of a considerable degree of heterogeneity in the phosphorylation state of rat brain MAP1B. It appears that MAP1B can be phosphorylated at multiple sites that may be conventionally classified into at least two modes of phosphorylation. Mode I of phosphorylation induces significant upward shifts in the electrophoretic mobility of the protein, giving rise to "high" MAP1B isoforms, whereas the mode II of MAP1B phosphorylation does not greatly affect the electrophoretic mobility of the protein. These MAP1B phosphorylation modes are differentially regulated throughout development and show some regional specificity. Cytosolic MAP1B is highly phosphorylated both at mode I and mode II sites in the developing rat brain, as well as in the adult olfactory bulb, where axonal growth takes place. In most adult rat brain regions, cytosolic MAP1B is highly phosphorylated at mode II sites but largely dephosphorylated at certain mode I sites. However, MAP1B present in the particulate fraction of most rat brain region homogenates may be partially dephosphorylated at certain mode II sites, although it contains some phosphorylated mode I sites. These data are compatible with the view that different protein kinases, possibly including casein kinase II and proline-directed protein kinases, might regulate the state of phosphorylation of MAP1B in distinct localizations along the development of different neuronal populations in the brain.

摘要

微管相关蛋白MAP1B的亚型模式及其针对一组磷酸化敏感表位的抗体的免疫反应性模式在不同的大鼠脑区有所不同,并且在发育过程中会发生变化。这表明大鼠脑MAP1B的磷酸化状态存在相当程度的异质性。似乎MAP1B可以在多个位点被磷酸化,这些位点通常可分为至少两种磷酸化模式。磷酸化模式I会导致该蛋白的电泳迁移率显著向上移动,产生“高”MAP1B亚型,而MAP1B的磷酸化模式II对该蛋白的电泳迁移率影响不大。这些MAP1B磷酸化模式在整个发育过程中受到不同的调节,并表现出一定的区域特异性。在发育中的大鼠脑以及成年嗅球(轴突生长发生的部位)中,胞质MAP1B在模式I和模式II位点均高度磷酸化。在大多数成年大鼠脑区,胞质MAP1B在模式II位点高度磷酸化,但在某些模式I位点大量去磷酸化。然而,大多数大鼠脑区匀浆颗粒部分中的MAP1B在某些模式II位点可能部分去磷酸化,尽管它含有一些磷酸化的模式I位点。这些数据与以下观点一致,即不同的蛋白激酶,可能包括酪蛋白激酶II和脯氨酸定向蛋白激酶,可能在大脑中不同神经元群体发育过程中的不同定位中调节MAP1B 的磷酸化状态。

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