ARF-Like (ARL) Proteins - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 234

Fig. 10.1 Summary of the cellular locations of members of the ARF family of regulatory
GTPases. Organelles (labeled in red text ) and GTPases ( green text ) are shown, based upon findings
described in the text. ARFs are included to highlight their co-localization at several organelles with
ARLs but are not described in the text
talk between those locations and functions in cells that is essential to the mainte-
nance of cell homeostasis or signaling.
Finally, we note a number of publications suggesting roles for different ARF
family members in aspects of viral or bacterial pathogenesis (Matto et al. 2011 ; van
der Linden et al. 2010 ; Yang et al. 2011 ) as well as human cancers (Louro
et al. 2004 ; Beghin et al. 2008 , 2009 ; Taniuchi et al. 2011 ) and inherited diseases
(Parisi and Glass 1993 ; Chiang et al. 2004 ; Fan et al. 2004 ; Cantagrel et al. 2008 ;
Cevik et al. 2010 ; Zhang et al. 2011b ; Thomas et al. submitted). In other RAS
superfamily GTPases, both the GTPase and its modulators (particularly GEFs and
GAPs) are linked to cancer or other human diseases (e.g., (Shannon et al. 1994 ;
Bollag et al. 1996 ). Similarly, as the modulators of ARLs are increasingly studied
they too are quickly being linked to human disease states (Chapple et al. 2001 ;
Hodgson et al. 2006 ; Veltel et al. 2008a ; Johnson et al. 2012 ; Jaworek et al. 2013 ).
The assay used to purify the first ARF used its role in cholera toxin action in vitro
(Schleifer et al. 1982 ; Kahn and Gilman 1984 ) and this was later found to extend
also to the closely related E. coli heat-labile toxin (Zhu and Kahn 2001 ;Zhu
et al. 2001 ). The use of ARF activity by bacterial toxins extends to Legionella
pneumophila , which encodes the RalF protein that contains the ARF GEF Sec7