Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling

作者：Wang, Juanfei; Ren, Jinqi; Wu, Bin; Feng, Shanshan; Cai, Guoping; Tuluc, Florin; Peranen, Johan; Guo, Wei^*

来源：Proceedings of the National Academy of Sciences, 2015, 112(1): 148-153.

DOI：10.1073/pnas.1412089112

• Rab GTPases
• Rab8
• guanine nucleotide exchange factor
• ERK
• phosphorylation

Exocytosis is tightly regulated in many cellular processes, from neurite expansion to tumor proliferation. Rab8, a member of the Rab family of small GTPases, plays an important role in membrane trafficking from the trans-Golgi network and recycling endosomes to the plasma membrane. Rabin8 is a guanine nucleotide exchange factor (GEF) and major activator of Rab8. Investigating how Rabin8 is activated in cells is thus pivotal to the understanding of the regulation of exocytosis. Here we show that phosphorylation serves as an important mechanism for Rabin8 activation. We identified Rabin8 as a direct phospho-substrate of ERK1/2 in response to EGF signaling. At the molecular level, ERK phosphorylation relieves the autoinhibition of Rabin8, thus promoting its GEF activity. We further demonstrate that blocking ERK1/2-mediated phosphorylation of Rabin8 inhibits transferrin recycling to the plasma membrane. Together, our results suggest that ERK1/2 activate Rabin8 to regulate vesicular trafficking to the plasma membrane in response to extracellular signaling.

• 出版日期2015-1-6
• 单位清华大学