TY - JOUR
T1 - Characterization of the tyrosine phosphorylation and distribution of dystrobrevin isoforms
AU - Balasubramanian, Sudha
AU - Fung, Eric T.
AU - Huganir, Richard L.
N1 - Funding Information:
We would like to thank Carol W. Doherty for her excellent technical assistance, Dr. Stanley Froehner for his generous gift of anti-syntrophin antibody, Michael Ehlers, Sunjeev Kamboj for critical reading of the manuscript and Doreen L. Bury for her excellent assistance in its preparation. This research was sponsored by an award from the National Institutes of Health, NS24418.
PY - 1998/8/7
Y1 - 1998/8/7
N2 - 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. Copyright (C) 1998 Federation of European Biochemical Societies.
AB - 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. Copyright (C) 1998 Federation of European Biochemical Societies.
KW - Dystrobrevin
KW - Neuromuscular junction
KW - Tyrosine phosphorylation
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U2 - 10.1016/S0014-5793(98)00804-7
DO - 10.1016/S0014-5793(98)00804-7
M3 - Article
C2 - 9720911
AN - SCOPUS:0031718526
SN - 0014-5793
VL - 432
SP - 133
EP - 140
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -