Characterization of the tyrosine phosphorylation and distribution of dystrobrevin isoforms

FEBS Letters

Fung, Eric T²  Balasubramanian, Sudha²  Huganir, Richard L¹ 

[1] Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Department of Neuroscience, 725 North Wolfe Street, 904A PCTB, Baltimore, MD 21205-2185, USA;Johns Hopkins University School of Medicine, Department of Neuroscience, 725 North Wolfe Street, 904A PCTB, Baltimore, MD 21205-2185, USA

关键词: Neuromuscular junction;    Dystrobrevin;    Tyrosine phosphorylation;   

DOI  :  10.1016/S0014-5793(98)00804-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Dystrobrevin, a member of the dystrophin family of proteins, was initially identified as a major tyrosine phosphorylated synaptic protein in the electric organ of Torpedo californica. In this paper, we show that the major sites of tyrosine phosphorylation of Torpedo dystrobrevin are within its C-terminus, on Tyr-693 and Tyr-710. Cloning of the mammalian homologue of dystrobrevin has recently shown that this phosphotyrosine containing tail, or PYCT, is subject to alternative splicing. To compare the expression and distribution of PYCT⁻ and PYCT⁺ splice variants, we generated antibodies against different regions of dystrobrevin. Here we show that the PYCT⁻ isoform of 62 kDa is expressed at high levels in all tissues examined. In contrast, PYCT⁺ isoforms are expressed primarily in brain and muscle, where they are concentrated at synapses. Moreover, PYCT⁺ isoforms associate more tightly with the membrane and with syntrophin, another synaptically enriched protein. These results suggest that PYCT⁺ isoforms of dystrobrevin are specialized components of the dystroglycan complex which render the complex sensitive to regulation by tyrosine kinases.

【 授权许可】

Unknown