Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2.

Research output: Contribution to journalArticle

Standard

Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2. / Hughes, Craig; Auger, Jocelyn; McGlade, J; Eble, JA; Pearce, AC; Watson, Steve.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 12, 01.12.2008, p. 2152-9.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Bibtex

@article{0c719d10111f4951be6214618920619e,
title = "Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2.",
abstract = "Background: The adapter proteins SLP-76 and LAT have been shown to play critical roles in the activation of PLCc2 in platelets downstream of GPVI/FcRc and the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation of SLP-76. Objective: In the present study, we have compared the role of Gads alongside that of LAT following activation of the major platelet glycoprotein receptors using mice deficient in the two adapter proteins. Results: Gads was found to be required for the efficient onset of aggregation and secretion in response to submaximal stimulation of GPVI and CLEC-2, but to be dispensable for activation following stronger stimulation of the two receptors. Gads was also dispensable for spreading induced through integrin aIIbb3 or the GPIb–IX–V complex.Further, Gads plays a negligible role in aggregate formation on collagen at an arteriolar rate of shear. In stark contrast, platelets deficient in the adapter LAT exhibit a marked decrease in aggregation and secretion following activation of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at arteriolar shear. Conclusions: The results demonstrate that Gads plays a key role in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and CLEC-2 whereas LAT is required for full activation over a wider range of agonist concentrations. These results reveal the presence of a Gads-independent pathway of platelet activation downstream of LAT.",
keywords = "signalosome, LAT, CLEC-2, platelet, GPVI, SLP-76, Gads",
author = "Craig Hughes and Jocelyn Auger and J McGlade and JA Eble and AC Pearce and Steve Watson",
year = "2008",
month = dec,
day = "1",
doi = "10.1111/j.1538-7836.2008.03166.x",
language = "English",
volume = "6",
pages = "2152--9",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley",
number = "12",

}

RIS

TY - JOUR

T1 - Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2.

AU - Hughes, Craig

AU - Auger, Jocelyn

AU - McGlade, J

AU - Eble, JA

AU - Pearce, AC

AU - Watson, Steve

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Background: The adapter proteins SLP-76 and LAT have been shown to play critical roles in the activation of PLCc2 in platelets downstream of GPVI/FcRc and the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation of SLP-76. Objective: In the present study, we have compared the role of Gads alongside that of LAT following activation of the major platelet glycoprotein receptors using mice deficient in the two adapter proteins. Results: Gads was found to be required for the efficient onset of aggregation and secretion in response to submaximal stimulation of GPVI and CLEC-2, but to be dispensable for activation following stronger stimulation of the two receptors. Gads was also dispensable for spreading induced through integrin aIIbb3 or the GPIb–IX–V complex.Further, Gads plays a negligible role in aggregate formation on collagen at an arteriolar rate of shear. In stark contrast, platelets deficient in the adapter LAT exhibit a marked decrease in aggregation and secretion following activation of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at arteriolar shear. Conclusions: The results demonstrate that Gads plays a key role in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and CLEC-2 whereas LAT is required for full activation over a wider range of agonist concentrations. These results reveal the presence of a Gads-independent pathway of platelet activation downstream of LAT.

AB - Background: The adapter proteins SLP-76 and LAT have been shown to play critical roles in the activation of PLCc2 in platelets downstream of GPVI/FcRc and the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation of SLP-76. Objective: In the present study, we have compared the role of Gads alongside that of LAT following activation of the major platelet glycoprotein receptors using mice deficient in the two adapter proteins. Results: Gads was found to be required for the efficient onset of aggregation and secretion in response to submaximal stimulation of GPVI and CLEC-2, but to be dispensable for activation following stronger stimulation of the two receptors. Gads was also dispensable for spreading induced through integrin aIIbb3 or the GPIb–IX–V complex.Further, Gads plays a negligible role in aggregate formation on collagen at an arteriolar rate of shear. In stark contrast, platelets deficient in the adapter LAT exhibit a marked decrease in aggregation and secretion following activation of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at arteriolar shear. Conclusions: The results demonstrate that Gads plays a key role in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and CLEC-2 whereas LAT is required for full activation over a wider range of agonist concentrations. These results reveal the presence of a Gads-independent pathway of platelet activation downstream of LAT.

KW - signalosome

KW - LAT

KW - CLEC-2

KW - platelet

KW - GPVI

KW - SLP-76

KW - Gads

U2 - 10.1111/j.1538-7836.2008.03166.x

DO - 10.1111/j.1538-7836.2008.03166.x

M3 - Article

C2 - 18826392

VL - 6

SP - 2152

EP - 2159

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 12

ER -