Novel functions of the phospholipase D2-phox homology domain in protein kinase C zeta activation
SCIE
SCOPUS
- Title
- Novel functions of the phospholipase D2-phox homology domain in protein kinase C zeta activation
- Authors
- Kim, JH; Kim, JH; Ohba, M; Suh, PG; Ryu, SH
- Date Issued
- 2005-04
- Publisher
- AMER SOC MICROBIOLOGY
- Abstract
- It has been established that protein kinase C zeta (PKC zeta) participates in diverse signaling pathways and cellular functions in a wide variety of cells, exhibiting properties relevant to cellular survival and proliferation. Currently, however, the regulation mechanism of PKC zeta remains elusive. Here, for the first time, we determine that phospholipase D2 (PLD2) enhances PKC zeta activity through direct interaction in a lipase activity-independent manner. This interaction of the PLD2-Phox homology (PX) domain with the PKC zeta-kinase domain also induces the activation loop phosphorylation of PKC zeta and downstream signal stimulation, as measured by p70 S6 kinase phosphorylation. Furthermore, only the PLD2-PX domain directly stimulates PKC zeta activity in vitro, and it is necessary for the formation of the ternary complex with phosphoinositide-dependent kinase I and PKC zeta. The mutant that substitutes the triple lysine residues (Lys(101), Lys(102), and LYS103) within the PLD2-PX domain with alanine abolishes interaction with the PKC zeta-kinase domain and activation of PKC zeta. Moreover, breast cancer cell viability is significantly affected by PLD2 silencing. Taken together, these results suggest that the PLD2-mediated PKC zeta activation is induced by its PX domain performing both direct activation of PKC zeta and assistance of activation loop phosphorylation. Furthermore, we find it is an important factor in the survival of breast cancer cells.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/24672
- DOI
- 10.1128/MCB.25.8.3194-3208.2005
- ISSN
- 0270-7306
- Article Type
- Article
- Citation
- MOLECULAR AND CELLULAR BIOLOGY, vol. 25, no. 8, page. 3194 - 3208, 2005-04
- Files in This Item:
-
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.