Adhesion of Neutrophils to Fibronectin: Role of the CD66 Antigens

Nair, K. U.; Zingde, Surekha M.

doi:10.1006/cimm.2001.1772

Cited by 54 publications

(38 citation statements)

References 34 publications

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“…In Lck-deficient T cells, CEACAM1 cannot be phosphorylated at tyrosine residues and consequently CEACAM1 lacks the ability to associate with SHP-1. This is consistent with previous observations that the tyrosines within the ITIMs of CEACAM1 can be phosphorylated by c-Src kinase in epithelial cells (29,32), Btk kinase in B cells (24), Lyn in neutrophils (38,39), and insulin receptor tyrosine kinase as well as epidermal growth factor receptor tyrosine kinase (40,41). Specific dependence on Lck for CEACAM1 tyrosine phosphorylation in T cells is consistent with a similar role for Lck in mediating tyrosine phosphorylation of Fc␥RIIb in NK cells (42).…”

Section: Discussionsupporting

confidence: 93%

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70

Chen

Qiao

et al. 2008

The Journal of Immunology

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The long cytoplasmic tail (CT) isoforms of carcinoembryonic Ag-related cell adhesion molecule 1 (CEACAM1) are expressed on activated human T cells and possess two ITIM motifs in the CT. These isoforms of CEACAM1 are inhibitory for T cell responses initiated by the TCR/CD3 complex with the inhibition dependent upon the ITIMs of CEACAM1 and Src homology 2 domain-containing phosphatase 1 (SHP-1). However, the mechanism by which this inhibition occurs in T cells is unknown. We demonstrate here that the Src family kinase, Lck, and the ability of CEACAM1 to bind homophilically are required for the ITIM phosphorylation of CEACAM1 that is a prerequisite for CEACAM1 association with SHP-1. We further show that CEACAM1 associates with and recruits SHP-1 to the TCR/CD3 complex leading to decreased phosphorylation of CD3-ζ and ZAP-70 and consequently decreased activation of the elements downstream of ZAP-70. This is physiologically relevant because extinction of SHP-1 expression or blockade of homophilic binding by CEACAM1 using a Fab that specifically recognizes the homophilic binding region of human CEACAM1 increases the cytolytic function initiated by the TCR/CD3 complex. These studies show that long CT isoforms of CEACAM1 orchestrate an inhibitory program that abrogates extremely proximal events downstream of the TCR/CD3 complex by focusing on the activation of ZAP-70.

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Section: Discussionsupporting

confidence: 93%

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70

Chen

Qiao

et al. 2008

The Journal of Immunology

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“…CD66b is a selective marker of neutrophils 16 that, also in our experiments, was found consistently negative in lymphocytes and monocytes (not shown). This screening system was selected to exclude from our analysis cells that could contaminate the flow cytometric neutrophil gate.…”

Section: Resultssupporting

confidence: 76%

Expression of CD4 on human peripheral blood neutrophils

Biswas¹,

Mantelli²,

Sica³

et al. 2003

Blood

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CD4, the primary receptor for entry of HIV, is known to be expressed on T cells and monocytes/macrophages; healthy natural killer (NK) lymphocytes; in vitro human herpesvirus 6 (HHV6)-infected CD8؉, NK, and ␥␦ T lymphocytes; CD34 ؉ progenitor cells; and a subset of eosinophils and basophils. We here report the unconventional expression of CD4 at the surface of peripheral blood neutrophils derived from 4 of 51 (7.8%) HIV-1-infected and 3 of 25 (12%) uninfected donors, with similar frequency within the 2 groups.The percentage of CD4 ؉ neutrophils ranged from 39% to 97% of the total neutrophil population. Both surface and cytoplasmic forms of CD4 were present in neutrophils. Quantitative RNA polymerase chain reaction (PCR) revealed that neutrophils contain levels of CD4 mRNA comparable to those of peripheral blood mononuclear cells derived from the same donor. The conformation of CD4 expressed at the surface of neutrophils was similar to that of CD4 expressed on T lymphocytes as determined by the bind- IntroductionCD4 was originally identified as a T-lymphocyte marker and specifically associated to the subset of helper T lymphocytes. In addition to its function as a ligand of major histocompatibility complex (MHC) class II molecules, 1 CD4 was defined as the primary receptor of HIV viruses. 2 Binding of HIV envelope to CD4 is the first event that allows its binding to other coreceptors, namely the chemokine receptors CCR5 and CXCR4, followed by membrane fusion and entry. 3,4 CD4 is also expressed on monocytes/ macrophages. 5 In addition, further studies have reported the expression of CD4 on cells other than helper T lymphocytes and monocytes, including eosinophils 6 ; CD34 ϩ progenitor cells 7,8 ; in vitro human herpesvirus 6 (HHV-6)-infected CD8 ϩ , 9 natural killer (NK), 10 and ␥␦ T lymphocytes 11 ; mast cells/basophils 12 ; and normal NK lymphocytes. 13 To our knowledge the presence of CD4 on peripheral blood neutrophils has not yet been documented.Traditionally, flow cytometry-based phenotyping is performed either on separated peripheral blood mononuclear cells or, in routine diagnostic investigation, on whole blood lymphocytes selected by morphologic gating; therefore, information regarding neutrophils is not gathered nor recorded. In our clinic we have set up whole blood-based flow cytometry protocols that analyze all leukocyte populations.By this mean we identified an HIV-infected patient (pt 1) whose neutrophils were unexpectedly stained by a CD4-specific monoclonal antibody (mAb). We, therefore, (1) attempted a preliminary evaluation of the frequency of individuals whose neutrophils display CD4, (2) confirmed the specificity by staining with mAb directed toward different conformational epitopes of CD4, (3) tested whether CD4 ϩ neutrophils could bind soluble HIV-1 envelope protein gp120, and (4) tested the endogenous origin of CD4 in neutrophils. Patients, materials, and methods PatientsFifty-one individuals infected with HIV were tested among patients with chronic HIV infection regularly followed at our ...

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“…Hck is expressed predominantly in granulocytic and monocytic cells (50,51), whereas ACK is broadly expressed in many cell types (17). Hck has been implicated in a wide variety of signaling pathways in hematopoietic cells, including phagocytosis and integrin-mediated signaling (52)(53)(54)(55)(56)(57). However, at present relatively few substrates or effectors of Hck have been identified.…”

Section: Discussionmentioning

confidence: 99%

Biochemical Properties of the Cdc42-associated Tyrosine Kinase ACK1

Yokoyama

Miller

2003

Journal of Biological Chemistry

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ACK1 (activated Cdc42-associated kinase 1) is a nonreceptor tyrosine kinase and the only tyrosine kinase known to interact with Cdc42. To characterize the enzymatic properties of ACK, we have expressed and purified active ACK using the baculovirus/Sf9 cell system. This ACK1 construct contains (from N to C terminus) the kinase catalytic domain, SH3 domain, and Cdc42-binding Cdc42/Rac interactive binding (CRIB) domain. We characterized the substrate specificity of ACK1 using synthetic peptides, and we show that the specificity of the ACK1 catalytic domain most closely resembles that of Abl. Purified ACK1 undergoes autophosphorylation, and autophosphorylation enhances kinase activity. We identified Tyr 284 in the activation loop of ACK1 as the primary autophosphorylation site using mass spectrometry. When expressed in COS-7 cells, the Y284F mutant ACK1 showed dramatically reduced levels of tyrosine phosphorylation. Although the SH3 and CRIB domains of purified ACK1 are able to bind ligands (a polyproline peptide and Cdc42, respectively), the addition of ligands did not stimulate tyrosine kinase activity. To characterize potential interacting partners for ACK1, we screened several SH2 and SH3 domains for their ability to bind to full-length ACK1 or to the catalytic-SH3-CRIB construct. ACK1 interacts most strongly with the SH3 domains of Src family kinases (Src or Hck) via its C-terminal proline-rich domain. Co-expression of Hck with kinase-inactive ACK1(K158R) in mammalian cells resulted in tyrosine phosphorylation of ACK1, suggesting that ACK1 is a substrate for Hck. Our data suggest that Hck is a novel binding partner for ACK1 that can regulate ACK1 activity by phosphorylation.Members of the Rho family of small GTP-binding proteins couple extracellular signals to the regulation of cell morphology, adhesion, differentiation, and proliferation (1-5). A number of proteins have been identified as targets for the Rho family proteins Rac and/or Cdc42, including p21-activated kinases (6 -8), Wiscott-Aldrich syndrome proteins (9 -11), mixed lineage kinases (12), and IQGAP (13-16). The ACK family nonreceptor tyrosine kinases (ACK1 and ACK2) associate specifically with Cdc42 and act as Cdc42 effectors in several signaling pathways (6,17,18). ACK1 has been reported to phosphorylate Dbl, a guanine nucleotide exchange factor toward Rho family proteins, thereby promoting Dbl activity. In this way, ACK1 is thought to act as a mediator of EGF 1 signals to Rho family GTP-binding proteins (19). ACK2 mediates cell adhesion signals initiated by integrin ␤ 1 in a Cdc42-dependent manner (20). ACKs interact directly with the clathrin heavy chain and participate in the regulation of receptor-mediated endocytosis (21, 22). However, the physiological functions as well as specific target molecules of ACKs are still incompletely understood.The domain structure of ACK kinases consists of an Nterminal tyrosine kinase catalytic domain followed by an SH3 domain, a Cdc42/Rac interactive binding (CRIB) domain, and a proline-rich region (see Fig. 1...

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Adhesion of Neutrophils to Fibronectin: Role of the CD66 Antigens

Cited by 54 publications

References 34 publications

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70

Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Inhibits Proximal TCR Signaling by Targeting ZAP-70

Expression of CD4 on human peripheral blood neutrophils

Biochemical Properties of the Cdc42-associated Tyrosine Kinase ACK1

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