共 45 条
A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1
被引:31
作者:
Kilisch, Markus
[1
]
Lytovchenko, Olga
[1
]
Arakel, Eric C.
[1
]
Bertinetti, Daniela
[2
]
Schwappach, Blanche
[1
,3
]
机构:
[1] Univ Med Gottingen, Dept Mol Biol, Humboldtallee 23, D-37073 Gottingen, Germany
[2] Univ Kassel, Dept Biochem, D-34132 Kassel, Germany
[3] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany
关键词:
14-3-3;
protein;
Endoplasmic reticulum;
Golgi;
Membrane trafficking;
Phosphorylation;
Two-pore-domain K+ channel;
COPI;
Protein kinase A;
TASK-1;
POTASSIUM CHANNELS TASK-1;
DEPENDENT PROTEIN-KINASE;
MEMBRANE-PROTEINS;
K+ CHANNELS;
TRANSPORT;
COATOMER;
SUBUNIT;
SIGNALS;
COPI;
D O I:
10.1242/jcs.180182
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
The transport of the K+ channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic.
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页码:831 / 842
页数:12
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