|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 April 2001, Vol. 97, No. 8, pp. 2351-2357
IMMUNOBIOLOGY
Inhibition of antigen-receptor signaling by Platelet Endothelial
Cell Adhesion Molecule-1 (CD31) requires functional ITIMs, SHP-2, and
p56lck
Debra K. Newman,
Christin Hamilton, and
Peter J. Newman
From the Blood Research Institute, The Blood Center of
Southeastern Wisconsin, Milwaukee, WI; and the Departments of
Microbiology, Pharmacology, and Cellular Biology, Medical College of
Wisconsin, Milwaukee, WI.
Platelet Endothelial Cell Adhesion Molecule-1
(PECAM-1, CD31) is a 130-kd member of the immunoglobulin gene
superfamily that is expressed on the surface of platelets, endothelial
cells, myeloid cells, and certain lymphocyte subsets. PECAM-1
has recently been shown to contain functional immunoreceptor
tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic
domain, and co-ligation of PECAM-1 with the T-cell antigen
receptor (TCR) results in tyrosine phosphorylation of
PECAM-1, recruitment of Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2), and
attenuation of TCR-mediated cellular signaling. To determine the
molecular basis of PECAM-1 inhibitory signaling in
lymphocytes, the study sought to (1) establish the importance of the
PECAM-1 ITIMs for its inhibitory activity, (2) determine
the relative importance of SHP-2 versus SHP-1 in mediating the
inhibitory effect of PECAM-1, and (3) identify the protein
tyrosine kinases required for PECAM-1 tyrosine
phosphorylation in T cells. Co-ligation of wild-type PECAM-1
with the B-cell antigen receptor expressed on chicken DT40 B cells
resulted in a marked reduction of calcium mobilization similar to
previous observations in T cells. In contrast, co-ligation of an
ITIM-less form of PECAM-1 had no inhibitory effect.
Furthermore, wild-type PECAM-1 was unable to attenuate
calcium mobilization in SHP-2-deficient DT40 variants despite abundant
levels of SHP-1 in these cells. Finally, PECAM-1 failed to
become tyrosine phosphorylated in p56lck-deficient Jurkat T
cells. Together, these data provide important insights into the
molecular requirements for PECAM-1 regulation of antigen
receptor signaling.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Wu, K. Tworkoski, M. Michaud, and J. A. Madri
Bone Marrow Monocyte PECAM-1 Deficiency Elicits Increased Osteoclastogenesis Resulting in Trabecular Bone Loss
J. Immunol.,
March 1, 2009;
182(5):
2672 - 2679.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-J. Chiu, E. McBeath, and K. Fujiwara
Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation
J. Cell Biol.,
August 25, 2008;
182(4):
753 - 763.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. O. Jurado, I. B. Alvarez, V. Pasquinelli, G. J. Martinez, M. F. Quiroga, E. Abbate, R. M. Musella, H. E. Chuluyan, and V. E. Garcia
Programmed Death (PD)-1:PD-Ligand 1/PD-Ligand 2 Pathway Inhibits T Cell Effector Functions during Human Tuberculosis
J. Immunol.,
July 1, 2008;
181(1):
116 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Munoz, M. Mittelbrunn, H. de la Fuente, M. Perez-Martinez, A. Garcia-Perez, A. Ariza-Veguillas, F. Malavasi, M. Zubiaur, F. Sanchez-Madrid, and J. Sancho
Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse
Blood,
April 1, 2008;
111(7):
3653 - 3664.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Rui, X. Liu, N. Li, Y. Jiang, G. Chen, X. Cao, and J. Wang
PECAM-1 Ligation Negatively Regulates TLR4 Signaling in Macrophages
J. Immunol.,
December 1, 2007;
179(11):
7344 - 7351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Yu, E. M. C. Chow, H. Wong, J. Gu, O. Mandelboim, S. D. Gray-Owen, and M. A. Ostrowski
CEACAM1 (CD66a) Promotes Human Monocyte Survival via a Phosphatidylinositol 3-Kinase- and AKT-dependent Pathway
J. Biol. Chem.,
December 22, 2006;
281(51):
39179 - 39193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Falati, S. Patil, P. L. Gross, M. Stapleton, G. Merrill-Skoloff, N. E. Barrett, K. L. Pixton, H. Weiler, B. Cooley, D. K. Newman, et al.
Platelet PECAM-1 inhibits thrombus formation in vivo
Blood,
January 15, 2006;
107(2):
535 - 541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. I. Ellyard, D. T. Avery, T. G. Phan, N. J. Hare, P. D. Hodgkin, and S. G. Tangye
Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow
Blood,
May 15, 2004;
103(10):
3805 - 3812.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Feng, J. A. Nagy, K. Pyne, H. F. Dvorak, and A. M. Dvorak
Ultrastructural Localization of Platelet Endothelial Cell Adhesion Molecule (PECAM-1, CD31) in Vascular Endothelium
J. Histochem. Cytochem.,
January 1, 2004;
52(1):
87 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Rathore, M. A. Stapleton, C. A. Hillery, R. R. Montgomery, T. C. Nichols, E. P. Merricks, D. K. Newman, and P. J. Newman
PECAM-1 negatively regulates GPIb/V/IX signaling in murine platelets
Blood,
November 15, 2003;
102(10):
3658 - 3664.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Verbrugge, T. d. Ruiter, H. Clevers, and L. Meyaard
Differential contribution of the immunoreceptor tyrosine-based inhibitory motifs of human leukocyte-associated Ig-like receptor-1 to inhibitory function and phosphatase recruitment
Int. Immunol.,
November 1, 2003;
15(11):
1349 - 1358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ferjoux, F. Lopez, J.-P. Esteve, A. Ferrand, E. Vivier, F. Vely, N. Saint-Laurent, L. Pradayrol, L. Buscail, and C. Susini
Critical Role of Src and SHP-2 in sst2 Somatostatin Receptor-mediated Activation of SHP-1 and Inhibition of Cell Proliferation
Mol. Biol. Cell,
September 1, 2003;
14(9):
3911 - 3928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. A. M. Relou, G. Gorter, I. A. Ferreira, H. J. M. van Rijn, and J.-W. N. Akkerman
Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Inhibits Low Density Lipoprotein-induced Signaling in Platelets
J. Biol. Chem.,
August 29, 2003;
278(35):
32638 - 32644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gao, W. Sun, M. Christofidou-Solomidou, M. Sawada, D. K. Newman, C. Bergom, S. M. Albelda, S. Matsuyama, and P. J. Newman
PECAM-1 functions as a specific and potent inhibitor of mitochondrial-dependent apoptosis
Blood,
July 1, 2003;
102(1):
169 - 179.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Newman and D. K. Newman
Signal Transduction Pathways Mediated by PECAM-1: New Roles for an Old Molecule in Platelet and Vascular Cell Biology
Arterioscler Thromb Vasc Biol,
June 1, 2003;
23(6):
953 - 964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-i. Yusa and K. S. Campbell
Src Homology Region 2-Containing Protein Tyrosine Phosphatase-2 (SHP-2) Can Play a Direct Role in the Inhibitory Function of Killer Cell Ig-Like Receptors in Human NK Cells
J. Immunol.,
May 1, 2003;
170(9):
4539 - 4547.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Righi, S. Deaglio, C. Pecchioni, A. Gregorini, A. L. Horenstein, G. Bussolati, A. Sapino, and F. Malavasi
Role of CD31/Platelet Endothelial Cell Adhesion Molecule-1 Expression in in Vitro and in Vivo Growth and Differentiation of Human Breast Cancer Cells
Am. J. Pathol.,
April 1, 2003;
162(4):
1163 - 1174.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Wilkinson, A. B. Lyons, D. Roberts, M.-X. Wong, P. A. Bartley, and D. E. Jackson
Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and autoimmune disease
Blood,
June 17, 2002;
100(1):
184 - 193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cicmil, J. M. Thomas, M. Leduc, C. Bon, and J. M. Gibbins
Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets
Blood,
January 1, 2002;
99(1):
137 - 144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. O. Goodwin, J. M. Mason, and S. I. Hajdu
Gene Expression Patterns of Paired Bronchioloalveolar Carcinoma and Benign Lung Tissue
Ann. Clin. Lab. Sci.,
October 1, 2001;
31(4):
369 - 375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Yamasaki, K. Nishida, M. Hibi, M. Sakuma, R. Shiina, A. Takeuchi, H. Ohnishi, T. Hirano, and T. Saito
Docking Protein Gab2 Is Phosphorylated by ZAP-70 and Negatively Regulates T Cell Receptor Signaling by Recruitment of Inhibitory Molecules
J. Biol. Chem.,
November 21, 2001;
276(48):
45175 - 45183.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
