FKBP12 Binds to Acylated H-Ras and Promotes Depalmitoylation

被引：93

作者：

Ahearn, Ian M. ^{[1
,2
,3
,4
]}

Tsai, Frederick D. ^{[1
,2
,3
,4
]}

Court, Helen ^{[1
,2
,3
,4
]}

Zhou, Mo ^{[1
,2
,3
,4
]}

Jennings, Benjamin C. ^{[5
]}

Ahmed, Mahiuddin ^{[6
]}

Fehrenbacher, Nicole ^{[1
,2
,3
,4
]}

Linder, Maurine E. ^{[5
]}

Philips, Mark R. ^{[1
,2
,3
,4
]}

机构：

[1] NYU, Langone Sch Med, Dept Med, New York, NY 10016 USA

[2] NYU, Langone Sch Med, Dept Cell Biol, New York, NY 10016 USA

[3] NYU, Langone Sch Med, Dept Pharmacol, New York, NY 10016 USA

[4] NYU, Langone Sch Med, NYU Canc Inst, New York, NY 10016 USA

[5] Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA

[6] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA

来源：

MOLECULAR CELL | 2011年 / 41卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CIS-TRANS ISOMERIZATION; PC12; CELLS; MOLECULAR TIMER; PLASMA-MEMBRANE; PROTEIN; PALMITOYLATION; LOCALIZATION; GOLGI; DIFFERENTIATION; CYCLOHEXIMIDE;

D O I：

10.1016/j.molcel.2011.01.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A cycle of palmitoylation/depalmitoylation of H-Ras mediates bidirectional trafficking between the Golgi apparatus and the plasma membrane, but nothing is known about how this cycle is regulated. We show that the prolyl isomerase (PI) FKBP12 binds to H-Ras in a palmitoylation-dependent fashion and promotes depalmitoylation. A variety of inhibitors of the PI activity of FKBP12, including FK506, rapamycin, and cycloheximide, increase steady-state palmitoylation. FK506 inhibits retrograde trafficking of H-Ras from the plasma membrane to the Golgi in a proline 179-dependent fashion, augments early GTP loading of Ras in response to growth factors, and promotes H-Ras-dependent neurite outgrowth from PC12 cells. These data demonstrate that FKBP12 regulates H-Ras trafficking by promoting depalmitoylation through cis-trans isomerization of a peptidyl-prolyl bond in proximity to the palmitoylated cysteines.

引用

页码：173 / 185

页数：13

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