Phosphorylation of protein kinase Cδ on distinct tyrosine residues regulates specific cellular functions
Phosphorylation of protein kinase Cδ on distinct tyrosine residues regulates specific cellular functions
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DOI：
10.1074/jbc.m005991200
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发表时间：
2000-11-10
影响因子：
4.8
通讯作者：
Brodie, C
中科院分区：
文献类型：
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作者：
Kronfeld, I;Kazimirsky, G;Brodie, C
蛋白激酶C δ（PKC δ）抑制C6胶质瘤细胞增殖并降低分化标志物谷氨酰胺合成酶（GS）的表达。在这里，我们报告，不同的，具体的酪氨酸残基PKC δ参与这两个反应。转染细胞与PKC δ突变在酪氨酸155苯丙氨酸引起增强的增殖反应12-佛波醇13-肉豆蔻酸酯，而GS的表达类似的PKC δ野生型转染子。相反，转染与PKC δ突变在酪氨酸187苯丙氨酸导致GS的表达增加，而增殖率类似的PKC δ野生型转染。PKC δ的酪氨酸磷酸化和血小板衍生生长因子（PDGF）诱导的GS表达减少被Src激酶抑制剂PP 1和PP 2消除。在对PDGF的反应中，Fyn通过酪氨酸187与PKC δ相关。最后，显性失活Fyn的过度表达消除了GS表达的减少，并减少了PDGF诱导的PKC δ的酪氨酸磷酸化。我们的结论是，酪氨酸磷酸化的PKC δ和它的协会与酪氨酸激酶可能是一个重要的分歧点在PKC信号。
Protein kinase C delta (PKC delta) inhibits proliferation and decreases expression of the differentiation marker glutamine synthetase (GS) in C6 glioma cells. Here, we report that distinct, specific tyrosine residues on PKC delta are involved in these two responses. Transfection of cells with PKC delta mutated at tyrosine 155 to phenylalanine caused enhanced proliferation in response to 12-phorbol la-myristate 13-acetate, whereas GS expression resembled that for the PKC delta wild-type transfectant. Conversely, transfection with PKC delta mutated at tyrosine 187 to phenylalanine resulted in increased expression of GS, whereas the rate of proliferation resembled that of the PKC delta wild-type transfectant. The tyrosine phosphorylation of PKC delta and the decrease in GS expression induced by platelet-derived growth factor (PDGF) were abolished by the Src kinase inhibitors PP1 and PP2. In response to PDGF, Fyn associated with PKC delta via tyrosine 187. Finally, overexpression of dominant negative Fyn abrogated the decrease in GS expression and reduced the tyrosine phosphorylation of PKC delta induced by PDGF. We conclude that the tyrosine phosphorylation of PKC delta and its association with tyrosine kinases may be an important point of divergence in PKC signaling.