Clifford A. Lowell

Convergence of immunoreceptor and integrin signaling (2007)

Abram, Clare L, Lowell, Clifford A

A common signaling pathway is known to operate downstream of immunoreceptors, such as the T-cell, B-cell, or Fc receptors, following engagement by their respective ligands. This pathway involves Src...

Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. (2005)

Hamerman, Jessica A, Tchao, Nadia K, Lowell, Clifford A, Lanier, Lewis L

DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of...

Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12 (2005)

Hamerman, Jessica A, Tchao, Nadia K, Lowell, Clifford A, Lanier, Lewis L

DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of...

A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase (2000)

Satterthwaite, Anne B., Willis, Fiona, Kanchanastit, Prim, Fruman, David, Cantley, Lewis C., Helgason, Cheryl D., ...

Modifier screens have been powerful genetic tools to define signaling pathways in lower organisms. The identification of modifier loci in mice has begun to allow a similar dissection of mammalian...

The sequence and structure of a new serum amyloid A gene (1986)

Stearman, Robert S., Lowell, Clifford A., Peltzman, Cynthia G., Morrow, John F.

The acute phase response is characterized by changes in the serum concentrations of many proteins. A 1000-fold increase in the concentration of ssrum amyloid A (SAA) protein occurs within 24 hours of...

Regulation of protein kinase CβI by two protein-tyrosine kinases, Btk and Syk

Kawakami, Yuko, Kitaura, Jiro, Hartman, Stephen E., Lowell, Clifford A., Siraganian, Reuben P., Kawakami, Toshiaki

Two protein-tyrosine kinases, Bruton's tyrosine kinase (Btk) and Syk, and members of the protein kinase C (PKC) subfamily of serine/threonine kinases play crucial roles in signal transduction through...

A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase

Satterthwaite, Anne B., Willis, Fiona, Kanchanastit, Prim, Fruman, David, Cantley, Lewis C., Helgason, Cheryl D., ...

Modifier screens have been powerful genetic tools to define signaling pathways in lower organisms. The identification of modifier loci in mice has begun to allow a similar dissection of mammalian...

Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr

Lowell, Clifford A., Berton, Giorgio

Signal transduction through the leukocyte integrins is required for the processes of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory reactions. Neutrophils isolated from...

Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI

Kitaura, Jiro, Song, Jinming, Tsai, Mindy, Asai, Koichi, Maeda-Yamamoto, Mari, Mocsai, Attila, ...

We demonstrate that binding of different IgE molecules (IgEs) to their receptor, FcεRI, induces a spectrum of activation events in the absence of a specific antigen and provide evidence that such...

Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src−/− mutant mice

Schwartzberg, Pamela L., Xing, Lianping, Hoffmann, Oskar, Lowell, Clifford A., Garrett, Lisa, Boyce, Brendan F., ...

The Src tyrosine kinase has been implicated in a wide variety of signal transduction pathways, yet despite the nearly ubiquitous expression of c-src, src−/− mice show only one major...

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

Mócsai, Attila, Humphrey, Mary Beth, Hu, Yongmei, Burghardt, Andrew, Spusta, Steven C., ...

Osteoclasts, the only bone-resorbing cells, are central to the pathogenesis of osteoporosis, yet their development and regulation are incompletely understood. Multiple receptors of the immune system...

Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Chou, Wen-Hai, Choi, Doo-Sup, Zhang, Hong, Mu, Dezhi, McMahon, Tom, Kharazia, Viktor N., ...

Thrombolysis is widely used to intervene in acute ischemic stroke, but reestablishment of circulation may paradoxically initiate a reperfusion injury. Here we describe studies with mice lacking...

Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12

Hamerman, Jessica A, Tchao, Nadia K, Lowell, Clifford A, Lanier, Lewis L

DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of...

Positive and Negative Regulation of Mast Cell Activation by Lyn via the Fc∊RI1

Xiao, Wenbin, Nishimoto, Hajime, Hong, Hong, Kitaura, Jiro, Nunomura, Satoshi, Maeda-Yamamoto, Mari, ...

Aggregation of the high affinity receptor for IgE (Fc∊RI) induces activation of mast cells. In this study we show that upon low intensity stimulation of Fc∊RI with monomeric IgE, IgE plus...

Regulation of Highly Cytokinergic IgE-Induced Mast Cell Adhesion by Src, Syk, Tec, and Protein Kinase C Family Kinases1

Kitaura, Jiro, Eto, Koji, Kinoshita, Tatsuya, Kawakami, Yuko, Leitges, Michael, Lowell, Clifford A., ...

Mast cells play a critical role in IgE-dependent immediate hypersensitivity. Recent studies have shown that, contrary to the traditional view, binding of monomeric IgE to Fc∊RI results in a number...

IgE- and IgE+Ag-mediated mast cell migration in an autocrine/paracrine fashion

Kitaura, Jiro, Kinoshita, Tatsuya, Matsumoto, Masaaki, Chung, Shaun, Kawakami, Yuko, Leitges, Michael, ...

Mast cells are the major effector cells for immediate hypersensitivity and chronic allergic reactions. These cells accumulate in mucosal tissues of allergic reactions, where immunoglobulin E (IgE) is...

Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury

Looney, Mark R., Su, Xiao, Van Ziffle, Jessica A., Lowell, Clifford A., Matthay, Michael A.

Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive...

Regulation of protein kinase CβI by two protein-tyrosine kinases, Btk and Syk

Kawakami, Yuko, Kitaura, Jiro, Hartman, Stephen E., Lowell, Clifford A., Siraganian, Reuben P., Kawakami, Toshiaki

Two protein-tyrosine kinases, Bruton's tyrosine kinase (Btk) and Syk, and members of the protein kinase C (PKC) subfamily of serine/threonine kinases play crucial roles in signal transduction through...

A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase

Satterthwaite, Anne B., Willis, Fiona, Kanchanastit, Prim, Fruman, David, Cantley, Lewis C., Helgason, Cheryl D., ...

Modifier screens have been powerful genetic tools to define signaling pathways in lower organisms. The identification of modifier loci in mice has begun to allow a similar dissection of mammalian...

Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr

Lowell, Clifford A., Berton, Giorgio

Signal transduction through the leukocyte integrins is required for the processes of firm adhesion, activation, and chemotaxis of neutrophils during inflammatory reactions. Neutrophils isolated from...

Evidence that IgE molecules mediate a spectrum of effects on mast cell survival and activation via aggregation of the FcεRI

Kitaura, Jiro, Song, Jinming, Tsai, Mindy, Asai, Koichi, Maeda-Yamamoto, Mari, Mocsai, Attila, ...

We demonstrate that binding of different IgE molecules (IgEs) to their receptor, FcεRI, induces a spectrum of activation events in the absence of a specific antigen and provide evidence that such...

Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src−/− mutant mice

Schwartzberg, Pamela L., Xing, Lianping, Hoffmann, Oskar, Lowell, Clifford A., Garrett, Lisa, Boyce, Brendan F., ...

The Src tyrosine kinase has been implicated in a wide variety of signal transduction pathways, yet despite the nearly ubiquitous expression of c-src, src−/− mice show only one major...

The immunomodulatory adapter proteins DAP12 and Fc receptor γ-chain (FcRγ) regulate development of functional osteoclasts through the Syk tyrosine kinase

Mócsai, Attila, Humphrey, Mary Beth, Hu, Yongmei, Burghardt, Andrew, Spusta, Steven C., ...

Osteoclasts, the only bone-resorbing cells, are central to the pathogenesis of osteoporosis, yet their development and regulation are incompletely understood. Multiple receptors of the immune system...

Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Chou, Wen-Hai, Choi, Doo-Sup, Zhang, Hong, Mu, Dezhi, McMahon, Tom, Kharazia, Viktor N., ...

Thrombolysis is widely used to intervene in acute ischemic stroke, but reestablishment of circulation may paradoxically initiate a reperfusion injury. Here we describe studies with mice lacking...

Neutrophils and their Fcγ receptors are essential in a mouse model of transfusion-related acute lung injury

Looney, Mark R., Su, Xiao, Van Ziffle, Jessica A., Lowell, Clifford A., Matthay, Michael A.

Transfusion-related acute lung injury (TRALI) is the most common cause of transfusion-related mortality. To explore the pathogenesis of TRALI, we developed an in vivo mouse model based on the passive...

Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production

Underhill, David M., Rossnagle, Eddie, Lowell, Clifford A., Simmons, Randi M.

Dectin-1 is a lectin receptor for β-glucan that is important for innate macrophage recognition of fungi and contributes to phagocytosis, reactive oxygen production, and induction of inflammatory...

G-CSF induced reactive oxygen species involves Lyn-PI3-kinase-Akt and contributes to myeloid cell growth

Zhu, Quan-sheng, Xia, Ling, Mills, Gordon B., Lowell, Clifford A., Touw, Ivo P., Corey, Seth J.

Granulocyte colony-stimulating factor (G-CSF) drives the production, survival, differentiation, and inflammatory functions of granulocytes. Reactive oxygen species (ROSs) provide a major thrust of...

Lyn kinase promotes erythroblast expansion and late-stage development

Karur, Vinit G., Lowell, Clifford A., Besmer, Peter, Agosti, Valter, Wojchowski, Don M.

Lyn kinase is known to modulate the formation and function of B cells, monocytes, and mast cells. However, Lyn-/- mice also develop erythrosplenomegaly, and cases for both negative and positive...

Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis

Mermel, Craig H., McLemore, Morgan L., Liu, Fulu, Pereira, Shalini, Woloszynek, Jill, Lowell, Clifford A., ...

Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. Truncation mutations of the G-CSF receptor (G-CSFR) are associated with the development of acute...

Neutrophil histamine contributes to inflammation in mycoplasma pneumonia

Xu, Xiang, Zhang, Dongji, Zhang, Hong, Wolters, Paul J., Killeen, Nigel P., Sullivan, Brandon M., ...

Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address...

Regulation of myeloproliferation and M2 macrophage programming in mice by Lyn/Hck, SHIP, and Stat5

Xiao, Wenbin, Hong, Hong, Kawakami, Yuko, Lowell, Clifford A., Kawakami, Toshiaki

The proliferation and differentiation of hematopoietic stem cells (HSCs) is finely regulated by extrinsic and intrinsic factors via various signaling pathways. Here we have shown that, similar to...

Src family kinases mediate neutrophil adhesion to adherent platelets

Evangelista, Virgilio, Pamuklar, Zehra, Piccoli, Antonio, Manarini, Stefano, Dell'Elba, Giuseppe, Pecce, Romina, ...

Polymorphonuclear leukocyte (PMN)–platelet interactions at sites of vascular damage contribute to local and systemic inflammation. We sought to determine the role of “outside-in” signaling by...

Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr

Gresham, Hattie D., Dale, Benjamin M., Potter, Jeffrey W., Chang, Peter W., Vines, Charlotte M., Lowell, Clifford A., ...

Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can...

Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

Fitzer-Attas, Cheryl J., Lowry, Malcolm, Crowley, Mary T., Finn, Alexander J., Meng, Fanying, DeFranco, Anthony L., ...

Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived...

Lipopolysaccharide (LPS)-induced Macrophage Activation and Signal Transduction in the Absence of Src-Family Kinases Hck, Fgr, and Lyn

Meng, Fanying, Lowell, Clifford A.

Lipopolysaccharide (LPS) stimulates immune responses by interacting with the membrane receptor CD14 to induce the generation of cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1,...

Independent and Opposing Roles For Btk and Lyn in B and Myeloid Signaling Pathways

Satterthwaite, Anne B., Lowell, Clifford A., Khan, Wasif N., Sideras, Paschalis, Alt, Frederick W., Witte, Owen N.

Transphosphorylation by Src family kinases is required for the activation of Bruton's tyrosine kinase (Btk). Differences in the phenotypes of Btk−/− and lyn−/− mice suggest that these kinases...

Coordinate interactions of Csk, Src, and Syk kinases with αIIbβ3 initiate integrin signaling to the cytoskeleton

Obergfell, Achim, Eto, Koji, Mocsai, Attila, Buensuceso, Charito, Moores, Sheri L., Brugge, Joan S., ...

Integrins regulate cell adhesion and motility through tyrosine kinases, but initiation of this process is poorly understood. We find here that Src associates constitutively with integrin αIIbβ3 in...

The Molecular Mechanism of B Cell Activation by toll-like Receptor Protein RP-105

Chan, Vivien W.F., Mecklenbräuker, Ingrid, Su, I-hsin, Texido, Gemma, Leitges, Michael, Carsetti, Rita, ...

The B cell–specific transmembrane protein RP-105 belongs to the family of Drosophila toll-like proteins which are likely to trigger innate immune responses in mice and man. Here we demonstrate that...

The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn

Hong, Hong, Kitaura, Jiro, Xiao, Wenbin, Horejsi, Vaclav, Ra, Chisei, Lowell, Clifford A., ...

IgE/antigen-dependent mast cell activation plays a central role in immediate hypersensitivity and other allergic reactions. The Src family tyrosine kinase (SFK) Lyn is activated by the cross-linking...

PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcRγ to induce slow leukocyte rolling

Zarbock, Alexander, Abram, Clare L., Hundt, Matthias, Altman, Amnon, Lowell, Clifford A., Ley, Klaus

E-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) can activate the β2 integrin lymphocyte function-associated antigen-1 by signaling through spleen tyrosine kinase (Syk). This...

Src family tyrosine kinase Lyn mediates VWF/GPIb-IX–induced platelet activation via the cGMP signaling pathway

Yin, Hong, Liu, Junling, Li, Zhenyu, Berndt, Michael C., Lowell, Clifford A., Du, Xiaoping

The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib-IX, mediates initial platelet adhesion and transmits signals leading to platelet activation. Src family tyrosine kinases...

Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase

Paul, Robert, Obermaier, Bianca, Van Ziffle, Jessica, Angele, Barbara, Pfister, Hans-Walter, Lowell, Clifford A., ...

Myeloid cells, including neutrophils and macrophages, play important roles in innate immune defense against acute bacterial infections. Myeloid Src family kinases (SFKs) p59/61hck (Hck), p58c-fgr...

The Absence of Hck, Fgr, and Lyn Tyrosine Kinases Augments Lung Innate Immune Responses to Pneumocystis murina▿

Nelson, Michael P., Metz, Allison E., Li, Shaoguang, Lowell, Clifford A., Steele, Chad

Src family tyrosine kinases (SFKs) phosphorylate immunotyrosine activation motifs in the cytoplasmic tail of multiple immunoreceptors, leading to the initiation of cellular effector functions, such...

Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury

Looney, Mark R., Nguyen, John X., Hu, Yongmei, Van Ziffle, Jessica A., Lowell, Clifford A., Matthay, Michael A.

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with...