DOI: 10.1084/jem.188.2.267. Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor γ Chain Complex on Human Platelets

Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor γ Chain Complex on Human Platelets

10.1084/jem.188.2.267

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

We have previously shown that uncharacterized glycoprotein VI (GPVI), which is constitutively associated and coexpressed with Fc receptor γ chain (FcRγ) in human platelets, is essential for collagen-stimulated tyrosine phosphorylation of FcRγ, Syk, and phospholipase Cγ2 (PLCγ2), leading to platelet activation. Here we investigated involvement of the Src family in the proximal signals through the GPVI–FcRγ complex, using the snake venom convulxin from Crotalus durissus terrificus, which specifically recognizes GPVI and activates platelets through cross-linking GPVI. Convulxin-coupled beads precipitated the GPVI–FcRγ complex from platelet lysates. Collagen and convulxin induced tyrosine phosphorylation of FcRγ, Syk, and PLCγ2 and recruited tyrosine-phosphorylated Syk to the GPVI–FcRγ complex. Using coprecipitation methods with convulxin-coupled beads and antibodies against FcRγ and the Src family, we showed that Fyn and Lyn, but not Yes, Src, Fgr, Hck, and Lck, were physically associated with the GPVI–FcRγ complex irrespective of stimulation. Furthermore, Fyn was rapidly activated by collagen or cross-linking GPVI. The Src family–specific inhibitor PP1 dose-dependently inhibited collagen- or convulxin-induced tyrosine phosphorylation of proteins including FcRγ, Syk, and PLCγ2, accompanied by a loss of aggregation and ATP release reaction. These results indicate that the Src family plays a critical role in platelet activation via the collagen receptor GPVI–FcRγ complex.

Bibliography

Ezumi, Y., Shindoh, K., Tsuji, M., & Takayama, H. (1998). Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor Î³ Chain Complex on Human Platelets. The Journal of Experimental Medicine, 188(2), 267â276.

Authors 4

Yasuharu Ezumi (first)
Keisuke Shindoh (additional)
Masaaki Tsuji (additional)
Hiroshi Takayama (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 5:14 a.m.)
Indexed	3 weeks, 6 days ago (Aug. 3, 2025, 7:07 p.m.)
Issued	27 years, 1 month ago (July 20, 1998)
Published	27 years, 1 month ago (July 20, 1998)
Published Online	27 years, 1 month ago (July 20, 1998)
Published Print	27 years, 1 month ago (July 20, 1998)

Funders 0

None

BibTeX

@article{Ezumi_1998, title={Physical and Functional Association of the Src Family Kinases Fyn and Lyn with the Collagen Receptor Glycoprotein VI-Fc Receptor γ Chain Complex on Human Platelets}, volume={188}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.188.2.267}, DOI={10.1084/jem.188.2.267}, number={2}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Ezumi, Yasuharu and Shindoh, Keisuke and Tsuji, Masaaki and Takayama, Hiroshi}, year={1998}, month=jul, pages={267–276} }

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  "abstract": "<jats:p>We have previously shown that uncharacterized glycoprotein VI (GPVI), which is constitutively associated and coexpressed with Fc receptor \u03b3 chain (FcR\u03b3) in human platelets, is essential for collagen-stimulated tyrosine phosphorylation of FcR\u03b3, Syk, and phospholipase C\u03b32 (PLC\u03b32), leading to platelet activation. Here we investigated involvement of the Src family in the proximal signals through the GPVI\u2013FcR\u03b3 complex, using the snake venom convulxin from Crotalus durissus terrificus, which specifically recognizes GPVI and activates platelets through cross-linking GPVI. Convulxin-coupled beads precipitated the GPVI\u2013FcR\u03b3 complex from platelet lysates. Collagen and convulxin induced tyrosine phosphorylation of FcR\u03b3, Syk, and PLC\u03b32 and recruited tyrosine-phosphorylated Syk to the GPVI\u2013FcR\u03b3 complex. Using coprecipitation methods with convulxin-coupled beads and antibodies against FcR\u03b3 and the Src family, we showed that Fyn and Lyn, but not Yes, Src, Fgr, Hck, and Lck, were physically associated with the GPVI\u2013FcR\u03b3 complex irrespective of stimulation. Furthermore, Fyn was rapidly activated by collagen or cross-linking GPVI. The Src family\u2013specific inhibitor PP1 dose-dependently inhibited collagen- or convulxin-induced tyrosine phosphorylation of proteins including FcR\u03b3, Syk, and PLC\u03b32, accompanied by a loss of aggregation and ATP release reaction. These results indicate that the Src family plays a critical role in platelet activation via the collagen receptor GPVI\u2013FcR\u03b3 complex.</jats:p>",
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