PMID- 16391519 OWN - NLM STAT- MEDLINE DCOM- 20060201 LR - 20211203 IS - 1226-3613 (Print) IS - 1226-3613 (Linking) VI - 37 IP - 6 DP - 2005 Dec 31 TI - Downstream components of RhoA required for signal pathway of superoxide formation during phagocytosis of serum opsonized zymosans in macrophages. PG - 575-87 AB - Rac1 and Rac2 are essential for the control of oxidative burst catalyzed by NADPH oxidase. It was also documented that Rho is associated with the superoxide burst reaction during phagocytosis of serum- (SOZ) and IgG-opsonized zymosan particles (IOZ). In this study, we attempted to reveal the signal pathway components in the superoxide formation regulated by Rho GTPase. Tat-C3 blocked superoxide production, suggesting that RhoA is essentially involved in superoxide formation during phagocytosis of SOZ. Conversely SOZ activated both RhoA and Rac1/2. Inhibition of RhoA-activated kinase (ROCK), an important downstream effector of RhoA, by Y27632 and myosin light chain kinase (MLCK) by ML-7 abrogated superoxide production by SOZ. Extracellular signaling-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) were activated during phagocytosis of SOZ, and Tat-C3 and SB203580 reduced ERK1/2 and p38 MAPK activation, suggesting that RhoA and p38 MAPK may be upstream regulators of ERK1/2. Inhibition of ERK1/2, p38 MAPK, phosphatidyl inositol 3-kinase did not block translocation of RhoA to membranes, suggesting that RhoA is upstream to these kinases. Inhibition of RhoA by Tat-C3 blocked phosphorylation of p47(PHOX). Taken together, RhoA, ROCK, p38MAPK, ERK1/2, and p47(PHOX) may be subsequently activated, leading to activation of NADPH oxidase to produce superoxide. FAU - Kim, Jun Sub AU - Kim JS AD - Department of Biochemistry, College of Medicine, Hallym University, Chuncheon 220-702, Korea. FAU - Kim, Jae Gyu AU - Kim JG FAU - Jeon, Chan Young AU - Jeon CY FAU - Won, Ha Young AU - Won HY FAU - Moon, Mi Young AU - Moon MY FAU - Seo, Ji Yeon AU - Seo JY FAU - Kim, Jong Il AU - Kim JI FAU - Kim, Jaebong AU - Kim J FAU - Lee, Jae Yong AU - Lee JY FAU - Choi, Soo Young AU - Choi SY FAU - Park, Jinseu AU - Park J FAU - Yoon Park, Jung Han AU - Yoon Park JH FAU - Ha, Kwon Soo AU - Ha KS FAU - Kim, Pyeung Hyeun AU - Kim PH FAU - Park, Jae Bong AU - Park JB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Exp Mol Med JT - Experimental & molecular medicine JID - 9607880 RN - 0 (Enzyme Inhibitors) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Macrophage-1 Antigen) RN - 0 (Opsonin Proteins) RN - 11062-77-4 (Superoxides) RN - 9010-72-4 (Zymosan) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (rho-Associated Kinases) RN - EC 2.7.11.18 (Myosin-Light-Chain Kinase) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Cell Line MH - Cell Membrane MH - Cytosol MH - Enzyme Inhibitors/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Macrophage-1 Antigen/pharmacology MH - Macrophages/drug effects/*metabolism/ultrastructure MH - Mice MH - Myosin-Light-Chain Kinase/metabolism MH - Opsonin Proteins/blood/*metabolism MH - *Phagocytosis MH - Protein Serine-Threonine Kinases/metabolism MH - Protein Transport MH - *Signal Transduction MH - Superoxides/*metabolism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Zymosan/*blood MH - p38 Mitogen-Activated Protein Kinases/metabolism MH - rho-Associated Kinases MH - rhoA GTP-Binding Protein/antagonists & inhibitors/*metabolism EDAT- 2006/01/05 09:00 MHDA- 2006/02/02 09:00 CRDT- 2006/01/05 09:00 PHST- 2006/01/05 09:00 [pubmed] PHST- 2006/02/02 09:00 [medline] PHST- 2006/01/05 09:00 [entrez] AID - 200512318 [pii] AID - 10.1038/emm.2005.71 [doi] PST - ppublish SO - Exp Mol Med. 2005 Dec 31;37(6):575-87. doi: 10.1038/emm.2005.71.