PMID- 22759969 OWN - NLM STAT- MEDLINE DCOM- 20121022 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 30 IP - 1 DP - 2012 TI - Store-operated Ca2+ entry (SOCE) plays a role in the polarization of neutrophil-like HL-60 cells by regulating the activation of Akt, Src, and Rho family GTPases. PG - 221-37 LID - 10.1159/000339059 [doi] AB - Neutrophil polarization is a basic activity involved in the innate immune response, and it may be initiated by extracellular Ca(2+) entry, a process primarily mediated through store-operated Ca(2+) entry (SOCE). Yet, the mechanisms by which SOCE participates in cell polarization remain unclear. We hypothesized that Akt- and Src-dependent pathways, traditionally linked to neutrophil polarization, may interact with SOCE in this event. In this study, SKF96365 and 2-APB, inhibitors of SOCE as proved by their inhibition on Mn(2+) influx, were observed to inhibit the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced influx of Ca(2+), the activation of Akt, Src, Rac1, Rac2, and Cdc42, and the polarization of differentiated HL-60 (dHL-60) cells. Downregulation of stromal interaction molecule 1 (STIM1), a Ca(2+) sensor identified to induce SOCE, by siRNA led to decreases in the following indexes: Ca(2+) entry, activation of Akt, Src, Rac2 (rather than Rac1) and Cdc42, and fMLP-induced polarization. This study suggests that SOCE might be the predominant form of Ca(2+) entry involved in the regulation of cell polarization, and it may act through the Akt/Src/Rac pathways, as modeled in dHL-60 cells. It also suggests that STIM1 is a key modulator of cell polarization, potentially serving as a target for the designation of anti-immune deficiency therapies. CI - Copyright (c) 2012 S. Karger AG, Basel. FAU - Zou, Wenying AU - Zou W AD - Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong, China. FAU - Meng, Xiaojing AU - Meng X FAU - Cai, Chunqing AU - Cai C FAU - Zou, Mengchen AU - Zou M FAU - Tang, Shihao AU - Tang S FAU - Chu, Xinwei AU - Chu X FAU - Wang, Xubu AU - Wang X FAU - Zou, Fei AU - Zou F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120619 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (Boron Compounds) RN - 0 (Calcium Channel Blockers) RN - 0 (Imidazoles) RN - 0 (Membrane Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (STIM1 protein, human) RN - 0 (Stromal Interaction Molecule 1) RN - 42Z2K6ZL8P (Manganese) RN - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine) RN - E4ES684O93 (2-aminoethoxydiphenyl borate) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - I61V87164A (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) SB - IM MH - Boron Compounds/pharmacology MH - Calcium Channel Blockers/pharmacology MH - *Calcium Signaling MH - *Cell Polarity MH - *Enzyme Activation MH - Gene Knockdown Techniques MH - HL-60 Cells MH - Humans MH - Imidazoles/pharmacology MH - Manganese/metabolism MH - Membrane Proteins/genetics/metabolism MH - N-Formylmethionine Leucyl-Phenylalanine/pharmacology MH - Neoplasm Proteins/genetics/metabolism MH - Neutrophils/*metabolism/physiology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA Interference MH - Stromal Interaction Molecule 1 MH - rho GTP-Binding Proteins/*metabolism MH - src-Family Kinases/*metabolism EDAT- 2012/07/05 06:00 MHDA- 2012/10/23 06:00 CRDT- 2012/07/05 06:00 PHST- 2012/05/14 00:00 [accepted] PHST- 2012/07/05 06:00 [entrez] PHST- 2012/07/05 06:00 [pubmed] PHST- 2012/10/23 06:00 [medline] AID - 000339059 [pii] AID - 10.1159/000339059 [doi] PST - ppublish SO - Cell Physiol Biochem. 2012;30(1):221-37. doi: 10.1159/000339059. Epub 2012 Jun 19.