ARF1-regulated coatomer directs the steady-state localization of protein kinase C epsilon at the Golgi apparatus

作者：Peterson Tabitha A; Stamnes Mark^*

来源：Biochimica et Biophysica Acta-Molecular Cell Research, 2013, 1833(3): 487-493.

DOI：10.1016/j.bbamcr.2012.11.011

• Protein kinase C
• Coatomer
• ADP-ribosylation factor-1 (ARF1)
• Receptor for activated C kinase-2 (RACK2)
• Golgi apparatus
• Phorbol ester

Protein kinase C epsilon (PKC epsilon) contributes to multiple signaling pathways affecting human disease. The function of PKC epsilon requires it to undergo changes in subcellular distribution in response to signaling events. While the mechanisms underlying this translocation are incompletely understood, it involves the receptor for activated C kinase protein (RACK2/beta%26apos;-COP). This receptor also functions as a vesicle coat protein in the secretory pathway where it is regulated by the small GTP-binding protein ADP-ribosylation factor, ARF1. We inhibited ARF1 activation to test the requirement for RACK2/beta%26apos;-COP in PKC epsilon localization in NIH3T3 fibroblasts. We found that steady-state localization of PKC epsilon at the Golgi complex requires ARF1-regulated RACK2/beta%26apos;-COP function. By contrast, we did not observe any defects in phorbol ester-induced translocation when ARF1 was inhibited. We also found that PKC epsilon bound to isolated membranes through two distinct mechanisms. One mechanism was dependent upon RACK2/beta%26apos;-COP while a second was RACK2/beta%26apos;-COP-independent and stimulated by phorbol esters. Finally, we show that RACK2/beta%26apos;-COP affects the subcellular distribution of a constitutively active form of PKC epsilon, in a manner similar to what we observed for wild-type PKC epsilon. Together, our data support a role for RACK2/beta%26apos;-COP in the steady-state localization of PKC epsilon at the Golgi apparatus, which may be independent of its role during PKC epsilon translocation to the cell surface.

• 出版日期2013-3