THE ALPHA-SUBUNIT OF THE HETEROTRIMERIC G-PROTEIN G(13) ACTIVATES A PHOSPHOLIPASE-D ISOZYME BY A PATHWAY REQUIRING RHO-FAMILY GTPASES

Citation
Sg. Plonk et al., THE ALPHA-SUBUNIT OF THE HETEROTRIMERIC G-PROTEIN G(13) ACTIVATES A PHOSPHOLIPASE-D ISOZYME BY A PATHWAY REQUIRING RHO-FAMILY GTPASES, The Journal of biological chemistry, 273(9), 1998, pp. 4823-4826
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0021-9258
Volume
273
Issue
9
Year of publication
1998
Pages
4823 - 4826
Database
ISI
SICI code
0021-9258(1998)273:9<4823:TAOTHG>2.0.ZU;2-0
Abstract
G(13) belongs to the G(12) family of heterotrimeric G proteins, whose effecters are poorly defined. The present study was designed to test i f phospholipase D (PLD) is regulated by G(13) and if Rho-type small GT Pases are involved. Expression of the constitutively active Q226L muta nt of the alpha-subunit of G(13) in COS-7 cells stimulated the activit y of a rat brain phospholipase D isozyme (rPLD1) co-expressed in the c ells. Wild type G alpha(13) was ineffective unless the cells were incu bated with AlF4-. rPLD1 was previously shown to be activated by consti tutively active V14RhoA in COS-7 cells (Park, S. K., Provost, J. J., B ae, C. D., Ho, W. T., and Exton, J. H. (1997) J. Biol. Chem. 272, 2926 3-29272). When the endogenous Rho proteins of the cells were inactivat ed by treatment with C3 exoenzyme from Clostridium botulinum, the abil ity of G alpha(13)Q226L to activate rPLD1 was greatly attenuated. Co-t ransfection of dominant negative N19RhoA and N17Rac-1, but not N17Cdc4 2Hs or N17Ras, also inhibited the activation. Expression of constituti vely active G alpha(q) in COS-7 cells also activated rPLD1, but consti tutively active forms of G alpha(i2) and G alpha(s) were without effec t. These findings support an effector role for PLD in G(13) signaling and demonstrate a requirement for Rho GTPases in this response.