Differential association of cytoplasmic signalling molecules SHP‐1, SHP‐2, SHIP and phospholipase C‐γ1 with PECAM‐1/CD31

Pumphrey, Nicholas J.; Taylor, Vanessa; Freeman, Sylvie; Douglas, Michael E.; Bradfield, Paul F.; Young, Stephen P.; Lord, Janet M.; Wakelam, Michael J.O.; Bird, Ian N.; Salmon, M; Buckley, Christopher D.

doi:10.1016/s0014-5793(99)00446-9

Cited by 101 publications

(76 citation statements)

References 33 publications

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“…23 Phosphorylation of these two tyrosine residues in PECAM-1 creates docking sites for the binding and activation of several cytosolic signaling molecules containing src homology-2 (SH2) domains. Included among the SH2-containing molecules that associate with PECAM-1 are the protein tyrosine phosphatases, SHP-1 and SHP-2, [24][25][26][27][28][29][30][31] the inosital phosphatase, SHIP 31 and phospholipase C-γ. 31 PECAM-1 may also associate with phosphoinositide 3-kinase 32 and β-or γ-catenin.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…Included among the SH2-containing molecules that associate with PECAM-1 are the protein tyrosine phosphatases, SHP-1 and SHP-2, [24][25][26][27][28][29][30][31] the inosital phosphatase, SHIP 31 and phospholipase C-γ. 31 PECAM-1 may also associate with phosphoinositide 3-kinase 32 and β-or γ-catenin. 33,34 The ability of PECAM-1 to bind to these various cytosolic molecules enables it to potentially modulate the activity of a number of intracellular signaling pathways.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

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Modulators of endothelial cell filopodia

DeLisser

2011

Cell Adhesion & Migration

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Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Modulators of endothelial cell filopodia

DeLisser

2011

Cell Adhesion & Migration

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“…The PECAM-1 cytoplasmic domain contains two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) centered around Tyr663 and Tyr686 that become phosphorylated in response to a variety of cellular activation events, after which they are able to recruit a number of Src homology 2 (SH2) domain-containing cytosolic signaling molecules, the best known of which is the protein-tyrosine phosphatase SHP-2 (Newman and Newman, 2003). Other SH2 domain-containing proteins that have been reported to associate with PECAM-1 include SHP-1 (Cao et al, 1998;Henshall et al, 2001;Hua et al, 1998;Pumphrey et al, 1999;Sagawa et al, 1997), Src family kinases (Lu et al, 1997;Masuda et al, 1997;Osawa et al, 1997), the inositol 5Ј-phosphatase SHIP-1 (Pumphrey et al, 1999) and phospholipase C1 (Henshall et al, 2001;Pumphrey et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity

Privratsky

Paddock

Florey

et al. 2011

Journal of Cell Science

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SummaryPECAM-1 (CD31) is a cellular adhesion and signaling receptor that is highly expressed at endothelial cell-cell junctions in confluent vascular beds. Previous studies have implicated PECAM-1 in the maintenance of vascular barrier integrity; however, the mechanisms behind PECAM-1-mediated barrier protection are still poorly understood. The goal of the present study, therefore, was to examine the pertinent biological properties of PECAM-1 (i.e. adhesion and/or signaling) that allow it to support barrier integrity. We found that, compared with PECAM-1-deficient endothelial cells, PECAM-1-expressing endothelial cell monolayers exhibit increased steady-state barrier function, as well as more rapid restoration of barrier integrity following thrombin-induced perturbation of the endothelial cell monolayer. The majority of PECAM-1-mediated barrier protection was found to be due to the ability of PECAM-1 to interact homophilically and become localized to cell-cell junctions, because a homophilic binding-crippled mutant form of PECAM-1 was unable to support efficient barrier function when re-expressed in cells. By contrast, cells expressing PECAM-1 variants lacking residues known to be involved in PECAM-1-mediated signal transduction exhibited normal to near-normal barrier integrity. Taken together, these studies suggest that PECAM-1-PECAM-1 homophilic interactions are more important than its signaling function for maintaining the integrity of endothelial cell junctions.

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“…A ITSM-like motif is situated 3-7 residues from the C terminus and is preceded by a conventional ITIM motif. Interestingly, similar to CD150ct, a GST platelet endothelial cell adhesion molecule/ CD31 cytoplasmic tail can bind both SHP-2 and SHIP, and SHIP interacts predominantly with the ITSM motif in CD31 (43).…”

Section: Modeling Of the Cd150ctmentioning

confidence: 99%

“…Using our model and SHP-2 structure revealed by crystallography (49), we predicted that simultaneous binding of Y281 and Y327 by two SHP-2 SH2 domains is unlikely, because the distance between tyrosine-binding pockets of N-and C-terminal domains of SHP-2 is 40 Å, compared with 8.18 Å, between Y281 and Y327 residues in CD150ct model. Moreover, it was shown that only the N-SH2, but not the C-SH2 domain of SHP-2 phosphopeptides binds to both ITIM-and ITSM-like motifs of CD31 (43).…”

Section: Modeling Of the Cd150ctmentioning

confidence: 99%

CD150 Association with Either the SH2-Containing Inositol Phosphatase or the SH2-Containing Protein Tyrosine Phosphatase Is Regulated by the Adaptor Protein SH2D1A

Shlapatska

Михалап

Berdova

et al. 2001

The Journal of Immunology

195

177

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CD150 (SLAM/IPO-3) is a cell surface receptor that, like the B cell receptor, CD40, and CD95, can transmit positive or negative signals. CD150 can associate with the SH2-containing inositol phosphatase (SHIP), the SH2-containing protein tyrosine phosphatase (SHP-2), and the adaptor protein SH2 domain protein 1A (SH2D1A/DSHP/SAP, also called Duncan’s disease SH2-protein (DSHP) or SLAM-associated protein (SAP)). Mutations in SH2D1A are found in X-linked lymphoproliferative syndrome and non-Hodgkin’s lymphomas. Here we report that SH2D1A is expressed in tonsillar B cells and in some B lymphoblastoid cell lines, where CD150 coprecipitates with SH2D1A and SHIP. However, in SH2D1A-negative B cell lines, including B cell lines from X-linked lymphoproliferative syndrome patients, CD150 associates only with SHP-2. SH2D1A protein levels are up-regulated by CD40 cross-linking and down-regulated by B cell receptor ligation. Using GST-fusion proteins with single replacements of tyrosine at Y269F, Y281F, Y307F, or Y327F in the CD150 cytoplasmic tail, we found that the same phosphorylated Y281 and Y327 are essential for both SHP-2 and SHIP binding. The presence of SH2D1A facilitates binding of SHIP to CD150. Apparently, SH2D1A may function as a regulator of alternative interactions of CD150 with SHP-2 or SHIP via a novel TxYxxV/I motif (immunoreceptor tyrosine-based switch motif (ITSM)). Multiple sequence alignments revealed the presence of this TxYxxV/I motif not only in CD2 subfamily members but also in the cytoplasmic domains of the members of the SHP-2 substrate 1, sialic acid-binding Ig-like lectin, carcinoembryonic Ag, and leukocyte-inhibitory receptor families.

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Differential association of cytoplasmic signalling molecules SHP‐1, SHP‐2, SHIP and phospholipase C‐γ1 with PECAM‐1/CD31

Cited by 101 publications

References 33 publications

Modulators of endothelial cell filopodia

Modulators of endothelial cell filopodia

Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity

CD150 Association with Either the SH2-Containing Inositol Phosphatase or the SH2-Containing Protein Tyrosine Phosphatase Is Regulated by the Adaptor Protein SH2D1A

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