Genomes and Genes
Gene Symbol: Cbl b
Description: Casitas B-lineage lymphoma b
Alias: AI429560, AI851073, Cbl-b, E3 ubiquitin-protein ligase CBL-B, RING-type E3 ubiquitin transferase CBL-B, SH3-binding protein CBL-B, casitas B-lineage lymphoma proto-oncogene b, signal transduction protein CBL-B
Products: Cbl b
- Wohlfert E, Callahan M, Clark R. Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice. J Immunol. 2004;173:1059-65 pubmed
- Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, et al. Ubiquitin ligase Cbl-b is a negative regulator for insulin-like growth factor 1 signaling during muscle atrophy caused by unloading. Mol Cell Biol. 2009;29:4798-811 pubmed publisher..The inhibition of Cbl-b-mediated ubiquitination may be a new therapeutic strategy for unloading-mediated muscle atrophy. ..
- Krawczyk C, Bachmaier K, Sasaki T, Jones R, Snapper S, Bouchard D, et al. Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells. Immunity. 2000;13:463-73 pubmed..Thus, Cbl-b functions as a negative regulator of receptor clustering and raft aggregation in T cells. ..
- Kitaura Y, Jang I, Wang Y, Han Y, Inazu T, Cadera E, et al. Control of the B cell-intrinsic tolerance programs by ubiquitin ligases Cbl and Cbl-b. Immunity. 2007;26:567-78 pubmed..Thus, Cbl proteins control B cell-intrinsic checkpoint of immune tolerance, possibly through coordinating multiple BCR-proximal signaling pathways during anergy induction. ..
- Fang N, Fang D, Wang H, Altman A, Liu Y. Regulation of immune responses by E3 ubiquitin-protein ligases. Curr Dir Autoimmun. 2002;5:161-75 pubmed
- Heissmeyer V, Macian F, Im S, Varma R, Feske S, Venuprasad K, et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol. 2004;5:255-65 pubmed..Our results define a complex molecular program that links gene transcription induced by calcium and calcineurin to a paradoxical impairment of signal transduction in anergic T cells. ..
- Bachmaier K, Krawczyk C, Kozieradzki I, Kong Y, Sasaki T, Oliveira dos Santos A, et al. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature. 2000;403:211-6 pubmed..Cbl-b is thus a key regulator of activation thresholds in mature lymphocytes and immunological tolerance and autoimmunity. ..
- Gruber T, Hermann Kleiter N, Hinterleitner R, Fresser F, Schneider R, Gastl G, et al. PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation. Sci Signal. 2009;2:ra30 pubmed publisher..Thus, our data establish a nonredundant antagonism between PKC-theta and Cbl-b that regulates T cell activation responses. ..
- Jeon M, Atfield A, Venuprasad K, Krawczyk C, Sarao R, Elly C, et al. Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity. 2004;21:167-77 pubmed..Our results show a critical role for Cbl-b in the regulation of peripheral tolerance and anergy of T cells. ..
- Qiao G, Lei M, Li Z, Sun Y, Minto A, Fu Y, et al. Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B. J Immunol. 2007;179:4473-9 pubmed..Together, our data suggest that Cbl-b attenuates CD40-mediated NF-kappaB and JNK activation, thereby suppressing B cell responses. ..
- Oksvold M, Dagger S, Thien C, Langdon W. The Cbl-b RING finger domain has a limited role in regulating inflammatory cytokine production by IgE-activated mast cells. Mol Immunol. 2008;45:925-36 pubmed..Thus the ability of Cbl-b to function as a negative regulator of FcvarepsilonRI signalling that promotes inflammatory cytokine production is largely independent of the RING finger domain. ..
- Gustin S, Thien C, Langdon W. Cbl-b is a negative regulator of inflammatory cytokines produced by IgE-activated mast cells. J Immunol. 2006;177:5980-9 pubmed..Thus, Cbl-b functions as a potent negative regulator of cytokines that promote allergic and inflammatory reactions. ..
- Krawczyk C, Jones R, Atfield A, Bachmaier K, Arya S, Odermatt B, et al. Differential control of CD28-regulated in vivo immunity by the E3 ligase Cbl-b. J Immunol. 2005;174:1472-8 pubmed..These data provide genetic evidence that CD28-dependent in vivo immune responses and Ig class switching can be genetically uncoupled from germinal center formation and ICOS induction by Cbl-b-Vav1-regulated signaling pathways. ..
- Kojo S, Elly C, Harada Y, Langdon W, Kronenberg M, Liu Y. Mechanisms of NKT cell anergy induction involve Cbl-b-promoted monoubiquitination of CARMA1. Proc Natl Acad Sci U S A. 2009;106:17847-51 pubmed publisher..The study identifies an important signaling pathway linking Cbl-b-induced monoubiquitination to NFkappaB activation in NKT cell anergy induction, which may help design approaches for human cancer therapy. ..
- Han C, Jin J, Xu S, Liu H, Li N, Cao X. Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b. Nat Immunol. 2010;11:734-42 pubmed publisher..Thus, TLR-triggered, active CD11b integrin engages in crosstalk with the MyD88 and TRIF pathways and subsequently inhibits TLR signaling in innate immune responses. ..
- Gronski M, Boulter J, Moskophidis D, Nguyen L, Holmberg K, Elford A, et al. TCR affinity and negative regulation limit autoimmunity. Nat Med. 2004;10:1234-9 pubmed..Therefore, autoimmune disease is sensitive both to the affinity of the activating ligand and to normal mechanisms that negatively regulate the immune response...
- Choi E, Orlova V, Fagerholm S, Nurmi S, Zhang L, Ballantyne C, et al. Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins. Blood. 2008;111:3607-14 pubmed publisher..In conclusion, Cbl-b deficiency activates LFA-1 and LFA-1-mediated inflammatory cell recruitment by stimulating the interaction between the LFA-1 beta-chain and 14-3-3 proteins. ..
- Carpino N, Turner S, Mekala D, Takahashi Y, Zang H, Geiger T, et al. Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity. 2004;20:37-46 pubmed..Therefore, Sts-1 and Sts-2 are critical regulators of the signaling pathways that regulate T cell activation. ..
- Abe T, Hirasaka K, Kagawa S, Kohno S, Ochi A, Utsunomiya K, et al. Cbl-b is a critical regulator of macrophage activation associated with obesity-induced insulin resistance in mice. Diabetes. 2013;62:1957-69 pubmed publisher..Therefore, inhibition of TLR4 signaling is an attractive therapeutic strategy for treatment of obesity-related insulin resistance. ..
- Yu J, Zhao H, Zhang Y, Liu Y, Yao L, Li X, et al. Ubiquitin ligase Cbl-b acts as a negative regulator in discoidin domain receptor 2 signaling via modulation of its stability. FEBS Lett. 2014;588:1509-14 pubmed publisher..Thus, Cbl-b, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway. ..
- Davidson D, Zhong M, Pandolfi P, Bolland S, Xavier R, Seed B, et al. The Csk-Associated Adaptor PAG Inhibits Effector T Cell Activation in Cooperation with Phosphatase PTPN22 and Dok Adaptors. Cell Rep. 2016;17:2776-2788 pubmed publisher..Thus, Csk-associating PAG is a critical component of the inhibitory machinery controlling effector T cell activation in cooperation with PTPN22 and Dok adaptors. ..
- Feng Q, Baird D, Peng X, Wang J, Ly T, Guan J, et al. Cool-1 functions as an essential regulatory node for EGF receptor- and Src-mediated cell growth. Nat Cell Biol. 2006;8:945-56 pubmed..These findings demonstrate that the regulated phosphorylation of Cool-1 is necessary to maintain the balance between normal signalling by EGFR and Src versus aberrant growth and transformation. ..
- Shen F, Lin Q, Gu Y, Childress C, Yang W. Activated Cdc42-associated kinase 1 is a component of EGF receptor signaling complex and regulates EGF receptor degradation. Mol Biol Cell. 2007;18:732-42 pubmed publisher..Taken together, our studies suggest that ACK1 senses signal of EGF and regulates ligand-induced degradation of EGFR...
- Huang F, Kitaura Y, Jang I, Naramura M, Kole H, Liu L, et al. Establishment of the major compatibility complex-dependent development of CD4+ and CD8+ T cells by the Cbl family proteins. Immunity. 2006;25:571-81 pubmed..They likely do so by suppressing MHC-independent NF-kappaB activation, possibly through downmodulating pre-TCR signaling in DP thymocytes. ..
- Shamim M, Nanjappa S, Singh A, Plisch E, Leblanc S, Walent J, et al. Cbl-b regulates antigen-induced TCR down-regulation and IFN-gamma production by effector CD8 T cells without affecting functional avidity. J Immunol. 2007;179:7233-43 pubmed..These findings have implications in the development of therapies to bolster CD8 T cell function during viral infections or suppress T cell-mediated immunopathology. ..
- Bhowmick S, Singh A, Flavell R, Clark R, O Rourke J, Cone R. The sympathetic nervous system modulates CD4(+)FoxP3(+) regulatory T cells via a TGF-beta-dependent mechanism. J Leukoc Biol. 2009;86:1275-83 pubmed publisher..Additionally, targeting Tregs via the SNS may be a novel approach to the prevention or treatment of autoimmune diseases...
- Zhu L, Luo T, Xu X, Guo Y, Zhao X, Wang T, et al. E3 ubiquitin ligase Cbl-b negatively regulates C-type lectin receptor-mediated antifungal innate immunity. J Exp Med. 2016;213:1555-70 pubmed publisher..Together, our study indicates that Cbl-b negatively regulates CLR-mediated antifungal innate immunity, which provides molecular insight for designing antifungal therapeutic agents. ..
- Stromnes I, Blattman J, Tan X, Jeevanjee S, Gu H, Greenberg P. Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice. J Clin Invest. 2010;120:3722-34 pubmed publisher..Thus, abrogating Cbl-b expression in effector T cells may improve the efficacy of adoptive therapy of some human malignancies. ..
- Huang H, Jeon M, Liao L, Yang C, Elly C, Yates J, et al. K33-linked polyubiquitination of T cell receptor-zeta regulates proteolysis-independent T cell signaling. Immunity. 2010;33:60-70 pubmed publisher..Thus, the present study reveals unconventional K33-linked polyubiquitination in nonproteolytic regulation of cell-surface-receptor-mediated signal transduction. ..
- Zeng S, Xu Z, Lipkowitz S, Longley J. Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl). Blood. 2005;105:226-32 pubmed..The activated KIT in turn induces phosphorylation and activation of Cbl proteins. The Cbl proteins then bind and direct the degradation of activated KIT, leading to down-regulation of KIT signaling. ..
- Xiao Y, Qiao G, Tang J, Tang R, Guo H, Warwar S, et al. Protein Tyrosine Phosphatase SHP-1 Modulates T Cell Responses by Controlling Cbl-b Degradation. J Immunol. 2015;195:4218-27 pubmed publisher..Therefore, SHP-1 regulates Cbl-b-mediated T cell responses by controlling its tyrosine phosphorylation and ubiquitination. ..
- Kohno S, Ueji T, Abe T, Nakao R, Hirasaka K, Oarada M, et al. Rantes secreted from macrophages disturbs skeletal muscle regeneration after cardiotoxin injection in Cbl-b-deficient mice. Muscle Nerve. 2011;43:223-9 pubmed publisher..Cbl-b is an important regulatory factor for cytotoxic T-cell infiltration via RANTES production in macrophages. ..
- Nakajima A, Sanjay A, Chiusaroli R, Adapala N, Neff L, Itzsteink C, et al. Loss of Cbl-b increases osteoclast bone-resorbing activity and induces osteopenia. J Bone Miner Res. 2009;24:1162-72 pubmed publisher..e., functions that cannot be compensated by the other homolog). One of Cbl-b's unique functions in osteoclasts is to downregulate bone resorption. ..
- WILSON B, Wang X, Shen X, McKenna E, Lemieux M, Cho Y, et al. Epigenetic antagonism between polycomb and SWI/SNF complexes during oncogenic transformation. Cancer Cell. 2010;18:316-28 pubmed publisher..Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss. ..
- Hundt M, Tabata H, Jeon M, Hayashi K, Tanaka Y, Krishna R, et al. Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect. Immunity. 2006;24:513-22 pubmed
- Zhang W, Shao Y, Fang D, Huang J, Jeon M, Liu Y. Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem. 2003;278:23978-83 pubmed..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. ..
- McGargill M, Wen B, Walsh C, Hedrick S. A deficiency in Drak2 results in a T cell hypersensitivity and an unexpected resistance to autoimmunity. Immunity. 2004;21:781-91 pubmed..These results expose a new pathway regulating T cell activation and highlight the intricacies of induced autoimmune disease. ..
- Harada Y, Harada Y, Elly C, Ying G, Paik J, Depinho R, et al. Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J Exp Med. 2010;207:1381-91 pubmed publisher..This study reveals that Foxo factors promote transcription of the Foxp3 gene in induced T reg cells, and thus provides new mechanistic insight into Foxo-mediated T cell regulation. ..
- Adapala N, Barbe M, Tsygankov A, Lorenzo J, Sanjay A. Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b. J Cell Biochem. 2014;115:1277-89 pubmed publisher..Hence, Cbl and Cbl-b play mutually exclusive roles in osteoclasts. Whereas Cbl-PI3K interaction regulates differentiation and survival, bone resorption is predominantly regulated by Cbl-b in osteoclasts. ..
- Wallner S, Lutz Nicoladoni C, Tripp C, Gastl G, Baier G, Penninger J, et al. The role of the e3 ligase cbl-B in murine dendritic cells. PLoS ONE. 2013;8:e65178 pubmed publisher..We conclude that in contrast to c-Cbl, Cbl-b plays only a limited role in the induction of Ag-specific T cell responses by murine BMDCs in vitro and in vivo...
- Bhowmick S, Clark R, Brocke S, Cone R. Antigen-specific splenic CD4+ and CD8+ regulatory T cells generated via the eye, suppress experimental autoimmune encephalomyelitis either at the priming or at the effector phase. Int Immunol. 2011;23:119-28 pubmed publisher..Hence, it is important to consider the phenotype of Treg cells while designing effective cell-based therapies against autoimmune disorders. ..
- Zhang R, Zhang N, Mueller D. Casitas B-lineage lymphoma b inhibits antigen recognition and slows cell cycle progression at late times during CD4+ T cell clonal expansion. J Immunol. 2008;181:5331-9 pubmed..These observations now suggest a novel role for Cbl-b in triggering the exit from cell cycle at the end of a CD4(+) T cell clonal expansion. ..
- Daniel J, Dangelmaier C, Mada S, Buitrago L, Jin J, Langdon W, et al. Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation. J Biol Chem. 2010;285:17282-91 pubmed publisher..These data indicate that Cbl-b plays a positive modulatory role in GPVI-dependent platelet signaling, which translates to an important regulatory role in hemostasis and thrombosis in vivo. ..
- Goetz B, An W, Mohapatra B, Zutshi N, Iseka F, Storck M, et al. A novel CBL-Bflox/flox mouse model allows tissue-selective fully conditional CBL/CBL-B double-knockout: CD4-Cre mediated CBL/CBL-B deletion occurs in both T-cells and hematopoietic stem cells. Oncotarget. 2016;7:51107-51123 pubmed publisher
- Zhang J, Chiang Y, Hodes R, Siraganian R. Inactivation of c-Cbl or Cbl-b differentially affects signaling from the high affinity IgE receptor. J Immunol. 2004;173:1811-8 pubmed..These results suggest that Cbl-b and c-Cbl have divergent effects on Fc epsilon RI signal transduction and that Cbl-b, but not c-Cbl, functions as a negative regulator of Fc epsilon RI-induced degranulation. ..
- Adapala N, Holland D, Scanlon V, Barbe M, Langdon W, Tsygankov A, et al. Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy. Bone. 2014;67:1-9 pubmed publisher..These data indicate that while lack of Cbl or Cbl-b distinctly affects bone remodeling, only the loss of Cbl-PI3K interaction protects mice from significant bone loss following ovariectomy. ..
- Cho J, Kim H, Ju Y, Kye Y, Lee G, Lee S, et al. CD45-mediated control of TCR tuning in naïve and memory CD8+ T cells. Nat Commun. 2016;7:13373 pubmed publisher..Inhibition by high CD45 on CD8+ T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens. ..
- Veselits M, Tanaka A, Lipkowitz S, O Neill S, Sciammas R, Finnegan A, et al. Recruitment of Cbl-b to B cell antigen receptor couples antigen recognition to Toll-like receptor 9 activation in late endosomes. PLoS ONE. 2014;9:e89792 pubmed publisher..These data indicate that Cbl-b acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9. ..
- Mohapatra B, Zutshi N, An W, Goetz B, Arya P, Bielecki T, et al. An essential role of CBL and CBL-B ubiquitin ligases in mammary stem cell maintenance. Development. 2017;144:1072-1086 pubmed publisher..Our studies reveal a novel, cell-autonomous requirement of CBL and CBL-B in epithelial stem cell maintenance during organ development and remodeling through modulation of mTOR signaling. ..
- Choi Y, Han Y, Lee S, Jin Y, Bahn M, Hur K, et al. Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix. Bone. 2015;75:201-9 pubmed publisher..Taken together, we propose novel regulatory roles of Cbl-b and c-Cbl during osteoblast differentiation in which Cbl-b and c-Cbl regulate the degradation of Osterix through the ubiquitin-proteasome pathway. ..
- McGargill M, Choy C, Wen B, Hedrick S. Drak2 regulates the survival of activated T cells and is required for organ-specific autoimmune disease. J Immunol. 2008;181:7593-605 pubmed..We present a model whereby T cell survival depends on a balance of TCR and costimulatory signals to explain how the absence of Drak2 affects autoimmune disease without generalized suppression of the immune system. ..
- Hoyne G, Flening E, Yabas M, Teh C, Altin J, Randall K, et al. Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes. J Immunol. 2011;186:2024-32 pubmed publisher..These results reveal a role for peripheral T cell anergy in organ-specific self-tolerance and illuminate the interplay between Cblb-dependent anergy and other mechanisms for preventing organ-specific autoimmunity. ..
- Zhou S, Chen W, Shi Z, Wang S, Li L, Wen X, et al. Silencing the expression of Cbl-b enhances the immune activation of T lymphocytes against RM-1 prostate cancer cells in vitro. J Chin Med Assoc. 2014;77:630-6 pubmed publisher..This study suggests a potentially novel immunotherapeutic strategy against prostate cancer. ..
- Pellegrini M, Calzascia T, Elford A, Shahinian A, Lin A, Dissanayake D, et al. Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med. 2009;15:528-36 pubmed publisher..The ability of adjuvant IL-7 to antagonize inhibitory networks at the cellular and molecular level has major implications for immunotherapy in the treatment of tumors. ..
- Zhao D, Zhang M, Wang M, Liu B, Wang X, Yang J, et al. Up-regulation of Cbl-b is associated with LSECtin-mediated inhibition of different CD4+ T-cell subsets. Immunobiology. 2013;218:602-8 pubmed publisher..Taken together, these data demonstrate that LSECtin-mediated signaling up-regulates the threshold of CD4(+) T cell activation via tuning the expression of Cbl-b. ..
- Ou R, Zhang M, Huang L, Moskophidis D. Control of virus-specific CD8+ T-cell exhaustion and immune-mediated pathology by E3 ubiquitin ligase Cbl-b during chronic viral infection. J Virol. 2008;82:3353-68 pubmed publisher..In conclusion, our results suggest that Cbl-b is critically involved in T-cell exhaustion and prevention of lethal disease. ..
- Paolino M, Thien C, Gruber T, Hinterleitner R, Baier G, Langdon W, et al. Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions. J Immunol. 2011;186:2138-47 pubmed publisher..Thus, modulation of the E3 ligase activity of Cbl-b might be a novel modality to control T cell immunity in vaccination, cancer biology, or autoimmunity. ..
- Liu Y, Li Y, Zhang L, Li M, Li C, Xue C, et al. NF-ÎºB downregulates Cbl-b through binding and suppressing Cbl-b promoter in T cell activation. J Immunol. 2015;194:3778-83 pubmed publisher..These results indicated that NF-ÎºB downregulated Cbl-b by binding and suppressing Cbl-b promoter in T cell activation. Our findings provide a novel role for NF-ÎºB signaling in T cell activation. ..
- Qiao G, Zhao Y, Li Z, Tang P, Langdon W, Yang T, et al. T cell activation threshold regulated by E3 ubiquitin ligase Cbl-b determines fate of inducible regulatory T cells. J Immunol. 2013;191:632-9 pubmed publisher..Furthermore, we show that Akt-2 but not Akt-1 regulates Foxp3 expression downstream of Cbl-b. Therefore, we demonstrate that Cbl-b regulates the fate of iTregs via controlling the threshold for T cell activation. ..
- Hirasaka K, Kohno S, Goto J, Furochi H, Mawatari K, Harada N, et al. Deficiency of Cbl-b gene enhances infiltration and activation of macrophages in adipose tissue and causes peripheral insulin resistance in mice. Diabetes. 2007;56:2511-22 pubmed..Cbl-b is a negative regulator of macrophage infiltration and activation, and macrophage activation by Cbl-b deficiency contributes to the peripheral insulin resistance and glucose intolerance via cytokines secreted from macrophages. ..
- Naramura M, Jang I, Kole H, Huang F, Haines D, Gu H. c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Nat Immunol. 2002;3:1192-9 pubmed..These findings show that Cbl family proteins negatively regulate T cell activation by promoting clearance of engaged TCR from the cell surface, a process that is apparently essential for the termination of TCR signals. ..
- Salingcarnboriboon R, Pavasant P, Noda M. Cbl-b enhances Runx2 protein stability and augments osteocalcin promoter activity in osteoblastic cell lines. J Cell Physiol. 2010;224:743-7 pubmed publisher..Moreover, the upregulation of downstream genes of Runx2 such as osteocalcin and alkaline phosphatase mRNA was also observed. These data propose the involvement of Cbl-b in the regulation of osteoblast-related genes expression. ..
- Yee N, Hamerman J. ?(2) integrins inhibit TLR responses by regulating NF-?B pathway and p38 MAPK activation. Eur J Immunol. 2013;43:779-92 pubmed publisher..Thus, ?(2) integrins limit TLR signaling by inhibiting NF-?B pathway activation and promoting p38 MAPK activation, thereby fine-tuning TLR-induced inflammatory responses. ..
- Balachandran P, Dragone L, Garrity Ryan L, Lemus A, Weiss A, Engel J. The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence. J Clin Invest. 2007;117:419-27 pubmed..To the best of our knowledge, this represents the first identification of a mammalian gene product that is specifically required for in vivo resistance to disease mediated by a type III-secreted effector. ..
- Zhang J, Bardos T, Li D, Gal I, Vermes C, Xu J, et al. Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J Immunol. 2002;169:2236-40 pubmed..Our results demonstrate that CD28 costimulation regulates the threshold for T cell activation, at least in part, by promoting Cbl-b ubiquitination and degradation. ..