Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway

Lynn S. Quek, Jean Max Pasquet, Ingeborg Hers, Richard Cornall, Graham Knight, Michael Barnes, Margaret L. Hibbs, Ashley R. Dunn, Clifford A. Lowell, Steve P. Watson

Research output: Contribution to journalArticleResearchpeer-review

111 Citations (Scopus)

Abstract

Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor γ (FcRγ chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn -/- platelets, tyrosine phosphorylation of FcRγ chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn -/- platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and α-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn -/- lyn -/- double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLCγ2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway.

Original languageEnglish
Pages (from-to)4246-4253
Number of pages8
JournalBlood
Volume96
Issue number13
Publication statusPublished - 1 Dec 2000

Cite this

Quek, L. S., Pasquet, J. M., Hers, I., Cornall, R., Knight, G., Barnes, M., ... Watson, S. P. (2000). Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway. Blood, 96(13), 4246-4253.
Quek, Lynn S. ; Pasquet, Jean Max ; Hers, Ingeborg ; Cornall, Richard ; Knight, Graham ; Barnes, Michael ; Hibbs, Margaret L. ; Dunn, Ashley R. ; Lowell, Clifford A. ; Watson, Steve P. / Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway. In: Blood. 2000 ; Vol. 96, No. 13. pp. 4246-4253.
@article{29aa9786a8984c70b134bd5ec02753c6,
title = "Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway",
abstract = "Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor γ (FcRγ chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn -/- platelets, tyrosine phosphorylation of FcRγ chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn -/- platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and α-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn -/- lyn -/- double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLCγ2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway.",
author = "Quek, {Lynn S.} and Pasquet, {Jean Max} and Ingeborg Hers and Richard Cornall and Graham Knight and Michael Barnes and Hibbs, {Margaret L.} and Dunn, {Ashley R.} and Lowell, {Clifford A.} and Watson, {Steve P.}",
year = "2000",
month = "12",
day = "1",
language = "English",
volume = "96",
pages = "4246--4253",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "13",

}

Quek, LS, Pasquet, JM, Hers, I, Cornall, R, Knight, G, Barnes, M, Hibbs, ML, Dunn, AR, Lowell, CA & Watson, SP 2000, 'Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway', Blood, vol. 96, no. 13, pp. 4246-4253.

Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway. / Quek, Lynn S.; Pasquet, Jean Max; Hers, Ingeborg; Cornall, Richard; Knight, Graham; Barnes, Michael; Hibbs, Margaret L.; Dunn, Ashley R.; Lowell, Clifford A.; Watson, Steve P.

In: Blood, Vol. 96, No. 13, 01.12.2000, p. 4246-4253.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Fyn and Lyn phosphorylate the Fc receptor γ chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway

AU - Quek, Lynn S.

AU - Pasquet, Jean Max

AU - Hers, Ingeborg

AU - Cornall, Richard

AU - Knight, Graham

AU - Barnes, Michael

AU - Hibbs, Margaret L.

AU - Dunn, Ashley R.

AU - Lowell, Clifford A.

AU - Watson, Steve P.

PY - 2000/12/1

Y1 - 2000/12/1

N2 - Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor γ (FcRγ chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn -/- platelets, tyrosine phosphorylation of FcRγ chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn -/- platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and α-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn -/- lyn -/- double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLCγ2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway.

AB - Activation of platelets by collagen is mediated by the complex glycoprotein VI (GPVI)/Fc receptor γ (FcRγ chain). In the current study, the role of 2 Src family kinases, Fyn and Lyn, in GPVI signaling has been examined using murine platelets deficient in one or both kinases. In the fyn -/- platelets, tyrosine phosphorylation of FcRγ chain, phopholipase C (PLC) activity, aggregation, and secretion are reduced, though the time of onset of response is unchanged. In the lyn -/- platelets, there is a delay of up to 30 seconds in the onset of tyrosine phosphorylation and functional responses, followed by recovery of phosphorylation and potentiation of aggregation and α-granule secretion. Tyrosine phosphorylation and aggregation in response to stimulation by collagen-related peptide is further attenuated and delayed in fyn -/- lyn -/- double-mutant platelets, and potentiation is not seen. This study provides the first genetic evidence that Fyn and Lyn mediate FcR immune receptor tyrosine-based activation motif phosphorylation and PLCγ2 activation after the ligation of GPVI. Lyn plays an additional role in inhibiting platelet activation through an uncharacterized inhibitory pathway.

UR - http://www.scopus.com/inward/record.url?scp=0034672357&partnerID=8YFLogxK

M3 - Article

VL - 96

SP - 4246

EP - 4253

JO - Blood

JF - Blood

SN - 0006-4971

IS - 13

ER -