RhoA GTPase regulates B cell receptor signaling.
ABSTRACT The RhoA GTPase controls many cellular functions, including gene transcription and actin polymerization. Several lines of evidence suggest that Rho GTPases are required for B cell receptor (BCR) signaling, but whether RhoA is necessary has not been investigated. Here, we show that RhoA is activated, downstream of PI3K, in response to BCR stimulation and is important for BCR-dependent calcium flux and cell proliferation. A RhoA dominant-negative mutant strongly inhibited BCR-dependent calcium mobilization. The RhoA-specific inhibitor, C3 toxin, inhibited both BCR-dependent calcium flux and cell proliferation. RhoA is important for BCR-dependent synthesis of IP(3) by PLCgamma2, but is not required for tyrosine phosphorylation of PLCgamma2. BCR-dependent synthesis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P(2)) is inhibited in the absence of RhoA function. Providing exogenous PtdIns-4,5-P(2) restores BCR-dependent calcium flux in cells lacking functional RhoA. Our findings support a function for RhoA in BCR-dependent PtdIns-4,5-P(2) synthesis, PLCgamma2 activation, calcium mobilization, and cell proliferation.
- SourceAvailable from: Chaogu Zheng
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- "RhoA-PI4P5K-PIP 2 pathway mediates CD146-induced ERM activation At the downstream of RhoA, Ser/Thr kinases Rhoassociated coiled-coil protein kinase (ROCK) and phosphatidylinositol-4-phosphate-5-kinase (PI4P5K) have been shown to regulate ERM phosphorylation and its interactions (Shibasaki et al., 1997; Matsui et al., 1999; Saci and Carpenter, 2005). Moreover, Rho- PI4P5K-PIP 2 pathway is responsible for continuous activation of ERM proteins. "
ABSTRACT: Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.Oncogene 07/2011; 31(3):306-21. DOI:10.1038/onc.2011.244 · 8.56 Impact Factor
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ABSTRACT: ABSTRACT One of the most versatile biological signalling entities is the calcium ion, Ca, binding domain,interacts with the membrane-bound,receptor glycophorin. Components,of the LPS-recognition system are essential to recruit Hly to the cell
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ABSTRACT: Rhythmic behaviors are a fundamental feature of all organisms. Pharyngeal pumping, the defecation cycle, and gonadal-sheath-cell contractions are three well-characterized rhythmic behaviors in the nematode C. elegans. The periodicities of the rhythms range from subsecond (pharynx) to seconds (gonadal sheath) to minutes (defecation). However, the molecular mechanisms underlying these rhythmic behaviors are not well understood. Here, we show that the C. elegans Rho/Rac-family guanine nucleotide exchange factor, VAV-1, which is homologous to the mammalian Vav proto-oncogene, has a crucial role in all three behaviors. vav-1 mutants die as larvae because VAV-1 function is required in the pharynx for synchronous contraction of the musculature. In addition, ovulation and the defecation cycle are abnormal and arrhythmic. We show that Rho/Rac-family GTPases and the signaling molecule inositol triphosphate (IP(3)) act downstream of VAV-1 signaling and that the VAV-1 pathway modulates rhythmic behaviors by dynamically regulating the concentration of intracellular Ca(2+).Cell 11/2005; 123(1):119-32. DOI:10.1016/j.cell.2005.08.001 · 33.12 Impact Factor