scholarly journals Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1855-1861
Author(s):  
SN Manie ◽  
A Astier ◽  
D Wang ◽  
JS Phifer ◽  
J Chen ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Multiple Substrates ◽  
Phosphorylated Proteins ◽  
Intracellular Signals ◽  
Cell Adhesion Molecule 1 ◽  
Alpha4 Beta7

B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105–130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105–125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.

scholarly journals Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 1855-1861 ◽  
Author(s):  
SN Manie ◽  
A Astier ◽  
D Wang ◽  
JS Phifer ◽  
J Chen ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Multiple Substrates ◽  
Phosphorylated Proteins ◽  
Intracellular Signals ◽  
Cell Adhesion Molecule 1 ◽  
Alpha4 Beta7

Abstract B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105–130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105–125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins.

Constitutive alternative NF-κB signaling promotes marginal zone B-cell development but disrupts the marginal sinus and induces HEV-like structures in the spleen

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2381-2389 ◽  
Author(s):  
Feng Guo ◽  
Debra Weih ◽  
Elke Meier ◽  
Falk Weih
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
B Cell ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Marginal Zone ◽  
Cell Development ◽  
B Cell Development ◽  
Marginal Sinus ◽  
Cell Adhesion Molecule 1

Nuclear factor-κB (NF-κB) plays a crucial role in B-cell and lymphoid organ development. Here, we studied the consequences of constitutive, signal-independent activation of the alternative NF-κB pathway for the splenic marginal zone (MZ). In contrast to nfkb2−/− mice, which lack both p100 and p52, mice that lack only the inhibitory p100 precursor but still express the p52 subunit of NF-κB2 (p100−/−) had markedly elevated MZ B-cell numbers. Both cell-intrinsic mechanisms and increased stromal expression of vascular cell adhesion molecule-1 (VCAM-1) contributed to the accumulation of MZ B cells in p100−/− spleens. While migration of p100−/− MZ B cells toward the lysophospholipid sphingosine-1 phosphate (S1P) was not affected, CXCL13-stimulated chemotaxis was impaired, correlating with reduced migration of MZ B cells into follicles in response to lipopolysaccharide (LPS). Strikingly, p100 deficiency resulted in the absence of a normal marginal sinus, strongly induced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and glycosylated cell adhesion molecule-1 (GlyCAM-1), and the formation of nonfunctional ectopic high endothelial venule (HEV)–like structures in the red pulp. Thus, constitutive activation of the alternative NF-κB pathway favors MZ B-cell development and accumulation but leads to a disorganized spleen microarchitecture.

scholarly journals Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets

Blood ◽  
2002 ◽  
Vol 99 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Milenko Cicmil ◽  
Joanne M. Thomas ◽  
Mireille Leduc ◽  
Cassian Bon ◽  
Jonathan M. Gibbins
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cross Linking ◽  
Endothelial Cell Adhesion Molecule ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a 130-kd transmembrane glycoprotein and a member of the growing family of receptors with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PECAM-1 is expressed on platelets, certain T cells, monocytes, neutrophils, and vascular endothelial cells and is involved in a range of cellular processes, though the role of PECAM-1 in platelets is unclear. Cross-linking of PECAM-1 results in phosphorylation of the ITIM allowing the recruitment of signaling proteins that bind by way of Src-homology domain 2 interactions. Proteins that have been implicated in the negative regulation of cellular activation by ITIM-bearing receptors include the tyrosine phosphatases SHP-1 and SHP-2. Tyrosine phosphorylation of immunoreceptor tyrosine-based activatory motif (ITAM)–bearing receptors such as the collagen receptor GPVI-Fc receptor γ-chain complex on platelets leads to activation. Increasing evidence suggests that ITIM- and ITAM-containing receptors may act antagonistically when expressed on the same cell. In this study it is demonstrated that cross-linking PECAM-1 inhibits the aggregation and secretion of platelets in response to collagen and the GPVI-selective agonist convulxin. In these experiments thrombin-mediated platelet aggregation and secretion were also reduced, albeit to a lesser degree than for collagen, suggesting that PECAM-1 function may not be restricted to the inhibition of ITAM-containing receptor pathways. PECAM-1 activation also inhibited platelet protein tyrosine phosphorylation stimulated by convulxin and thrombin; this was accompanied by inhibition of the mobilization of calcium from intracellular stores. These data suggest that PECAM-1 may play a role in the regulation of platelet function in vivo.

scholarly journals Evidence for a role of platelet endothelial cell adhesion molecule-1 in endothelial cell mechanosignal transduction

2002 ◽  
Vol 158 (4) ◽  
pp. 773-785 ◽  
Author(s):  
Masaki Osawa ◽  
Michitaka Masuda ◽  
Ken-ichi Kusano ◽  
Keigi Fujiwara
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Endothelial Cell Adhesion Molecule ◽  
Erk Phosphorylation ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion

Fluid shear stress (FSS) induces many forms of responses, including phosphorylation of extracellular signal–regulated kinase (ERK) in endothelial cells (ECs). We have earlier reported rapid tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1) in ECs exposed to FSS. Osmotic changes also induced similar PECAM-1 and ERK phosphorylation with nearly identical kinetics. Because both FSS and osmotic changes should mechanically perturb the cell membrane, they might activate the same mechanosignaling cascade. When PECAM-1 is tyrosine phosphorylated by FSS or osmotic changes, SHP-2 binds to it. Here we show that ERK phosphorylation by FSS or osmotic changes depends on PECAM-1 tyrosine phosphorylation, SHP-2 binding to phospho-PECAM-1, and SHP-2 phosphatase activity. In ECs under flow, detectable amounts of SHP-2 and Gab1 translocated from the cytoplasm to the EC junction. When magnetic beads coated with antibodies against the extracellular domain of PECAM-1 were attached to ECs and tugged by magnetic force for 10 min, PECAM-1 associated with the beads was tyrosine phosphorylated. ERK was also phosphorylated in these cells. Binding of the beads by itself or pulling on the cell surface using poly-l–coated beads did not induce phosphorylation of PECAM-1 and ERK. These results suggest that PECAM-1 is a mechanotransduction molecule.

Differential Expression of Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1) in Murine Tissues

1998 ◽  
Vol 5 (2-3) ◽  
pp. 179-188 ◽  
Author(s):  
MICHAEL J EPPIHIMER ◽  
J A N I C E RUSELL ◽  
R O B E R T LANGLEY ◽  
G I N A VALLIEN ◽  
DONALD C ANDERSON ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Differential Expression ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Endothelial Cell Adhesion Molecule ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Endothelial Cell Adhesion
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