Disease relevance of WKYMVm

• Furthermore, WKYMVm inhibited the infection of human peripheral monocyte-derived macrophages and CD4(+) T lymphocytes by R5 or X4 strains of HIV-1, respectively [1].
• Furthermore, when WKYMVm was codelivered with HIV, HBV and Influenza DNA vaccines, WKYMVm selectively enhanced the vaccine-induced CD8(+) T cell responses in a dose-dependent manner, in terms of IFN-gamma secretion and cytolytic activity [2].
• In this study, we observed that the stimulation of FPRL1 by Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) caused serine phosphorylation but not tyrosine phosphorylation of STAT3 in a pertussis toxin-sensitive manner [3].

High impact information on WKYMVm

• Both CXCR4 and CCR5 were desensitized by activation of the cells with WKYMVm via a staurosporine-sensitive pathway [1].
• The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1 [1].
• These results suggest that even though WKYMVm may bind FPR the cells are activated preferentially through a receptor distinct from the FPR [4].
• The costimulation of DCs with WKYMVm and LPS dramatically inhibited LPS-induced IL-12 production, CD86 and HLA-DR surface expression, and DC-mediated T cell proliferation [5].
• These findings demonstrate that WKYMVm inhibits DC maturation by LPS [5].

Biological context of WKYMVm

• Optimal chemotaxis was achieved with 1 nM of WKYMVm, but it required 100 nM of fMLF [6].
• WKYMVm stimulated rapid and potent phosphorylation of the mitogen-activated protein kinases extracellular signal-related kinases 1 and 2 when used at 50 nM [6].
• Competitive binding and desensitization data suggest that both peptides interact with the same receptor but may use nonoverlapping binding sites because WKYMVm was unable to effectively displace [(3)H]fMLF bound to mFPR [6].
• When monocytes were incubated with WKYMVm, caspase-3 activity, which is important for cell death, was inhibited [7].
• OBJECTIVES: Previously we reported that a synthetic peptide, WKYMVm, stimulates phosphoinositide (PI) hydrolysis in several hematopoietic cell lines and human neutrophils [8].

Anatomical context of WKYMVm

• The observation that exudated cells are primed in their response to WKYMVm suggests that FPRL1/LXA(4)R like FPR is stored in mobilizable organelles [4].
• Recently, a novel peptide (Trp-Lys-Tyr-Met-Val-D-Met, WKYMVm) has been shown to induce superoxide generation in human monocytes [9].
• In the study to characterize the receptor(s) for WKYMVm, we found that this peptide induced marked chemotaxis and calcium flux in human phagocytes [10].
• Our study suggests that FPR and FPRL1 in phagocytes react to a broad spectrum of agonists and WKYMVm as a remarkably potent agonist provides a valuable tool for studying leukocyte signaling via these receptors [10].
• Quin-C1 induces chemotaxis and secretion of beta-glucuronidase in peripheral blood neutrophils with a potency of approximately 1/1000 of that of the peptide agonist WKYMVm [11].

Associations of WKYMVm with other chemical compounds

• The WKYMVm activates FPRL1-expressing cells in a cyclosporin H-independent manner with an EC(50 )of around 75 pmol/L, whereas it activates FPR-expressing cells with an EC(50 )of around 25 nmol/L [4].
• WKYMVm also strongly stimulated LTB4 production in human neutrophils without affecting PGE(2) production, whereas SAA strongly stimulates cyclooxygenase-2 (COX-2) expression and PGE(2) production but not LTB4 production [12].
• The synthetic chemoattractant peptide WKYMVm induces superoxide production by human eosinophils via the phosphoinositide 3-kinase-mediated activation of ERK1/2 [13].
• RESULTS: WKYMVm-induced superoxide production by eosinophils was strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002 [13].
• Furthermore, ERK1/2 activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220 [13].

Gene context of WKYMVm

• While FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm, nanomolar concentrations of the peptide were required to induce migration of FPR-expressing cells [10].
• The two conformers similarly inhibited binding of (125)I-labeled WKYMVm to FPRL2-expressing cells (IC(50) approximately 2.5-3 micrometer) [14].
• To develop agonists that selectively activate phagocyte functions and therefore protect host from unwanted tissue damage, we generated various WKYMVm analogs and examined their effects on cellular responses in FPR- or FPRL1-expressing RBL-2H3 cells [15].
• Furthermore, the interrelationship between the two phospholipases, cPLA2 and PLD1, and upstream signaling molecules involved in WKYMVm-dependent activation was investigated [9].
• With respect to the molecular mechanisms involved in the differential action of SAA and WKYMVm, we found that SAA could not competitively inhibit the binding of 125I-labeled WKYMVm to FPRL1 [16].

Analytical, diagnostic and therapeutic context of WKYMVm

• In this study, we evaluate whether WKYMVm stimulates bactericidal activity in neutrophils obtained from patients who received chemotherapy for solid tumors when they were neutropenic [17].

References