期刊
BIOCHEMICAL JOURNAL
卷 398, 期 -, 页码 1-13出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20060565
关键词
ADP-ribosylation factor 1/6 (Arf1/Arf6); phosphatidylinositol phosphate kinase (PIPK); PtdIns(4,5)P-2; phosphatidic acid; Rho/Rac/Cdc42; small G-protein
资金
- NCI NIH HHS [R01CA104708, R01 CA104708] Funding Source: Medline
- NIGMS NIH HHS [R01 GM057549] Funding Source: Medline
Regulation of PIPK (phosphatidylinositol phosphate kinase) and PtdIns(4,5)P-2 signalling by small G-proteins and their effectors is key to many biological functions. Through selective recruitment and activation of different PIPK isoforms, small G-proteins such as Rho, Rac and Cdc42 modulate actin dynamics and cytoskeleton-dependent cellular events in response to extracellular signalling. These activities affect a number of processes, including endocytosis, bacterial penetration into host cells and cytolytic granule-mediated targeted cell killing. Small G-proteins and their modulators are also regulated by phosphoinositides through translocation and conformational changes. Arf family small G-proteins act at multiple sites as regulators of membrane trafficking and actin cytoskeletal remodelling, and regulate a feedback loop comprising phospholipase D, phosphatidic acid, PIPKs and PtdIns(4,5)P-2. contributing to enhancement of PtdIns(4,5)P-2-mediated cellular events and receptor signalling. Na+, Kir (inwardly rectifying K+), Ca2+ and TRP (transient receptor potential) ion channels are regulated by small G-proteins and membrane pools of PtdIns(4,5)P-2. Yeast phosphatidylinositol 4-phosphate 5-kinases Mss4 and Its3 are involved in resistance against disturbance of sphingolipid biosynthesis and maintenance of cell integrity through the synthesis of PtdIns(4,5)P-2 and downstream signalling through the Rom2/Rho2 and Rgf1/Rho pathways. Here, we review models for regulated intracellular targeting of PIPKs by small G-proteins and other modulators in response to extracellular signalling. We also describe the spatial and temporal cross-regulation of PIPKs and small G-proteins that is critical for a number of cellular functions.
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