WNT-3a modulates platelet function by regulating small GTPase activity

Brian M Steele; Matthew T Harper; Albert P Smolenski; Naheda Alkazemi; Alastair W Poole; Desmond J Fitzgerald; Patricia B Maguire

doi:10.1016/j.febslet.2012.05.060

WNT-3a modulates platelet function by regulating small GTPase activity

Brian M Steele, Matthew T Harper, Albert P Smolenski, Naheda Alkazemi, Alastair W Poole, Desmond J Fitzgerald, Patricia B Maguire

Research output: Contribution to journal › Article (Academic Journal) › peer-review

16 Citations (Scopus)

Abstract

Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.

Original language	English
Pages (from-to)	2267-72
Number of pages	6
Journal	FEBS Letters
Volume	586
Issue number	16
DOIs	https://doi.org/10.1016/j.febslet.2012.05.060
Publication status	Published - 30 Jul 2012

Bibliographical note

Keywords

Recombinant Proteins
Humans
Wnt3A Protein
rap GTP-Binding Proteins
Hydrolysis
Models, Biological
Guanosine Triphosphate
Blood Platelets
Adaptor Proteins, Signal Transducing
Extracellular Matrix
rac1 GTP-Binding Protein
Gene Expression Regulation
Monomeric GTP-Binding Proteins
cdc42 GTP-Binding Protein
Signal Transduction
Densitometry

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@article{7d1332647b584f22a2cf511537f270e5,

title = "WNT-3a modulates platelet function by regulating small GTPase activity",

abstract = "Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.",

keywords = "Recombinant Proteins, Humans, Wnt3A Protein, rap GTP-Binding Proteins, Hydrolysis, Models, Biological, Guanosine Triphosphate, Blood Platelets, Adaptor Proteins, Signal Transducing, Extracellular Matrix, rac1 GTP-Binding Protein, Gene Expression Regulation, Monomeric GTP-Binding Proteins, cdc42 GTP-Binding Protein, Signal Transduction, Densitometry",

author = "Steele, {Brian M} and Harper, {Matthew T} and Smolenski, {Albert P} and Naheda Alkazemi and Poole, {Alastair W} and Fitzgerald, {Desmond J} and Maguire, {Patricia B}",

year = "2012",

month = jul,

day = "30",

doi = "10.1016/j.febslet.2012.05.060",

language = "English",

volume = "586",

pages = "2267--72",

journal = "FEBS Letters",

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TY - JOUR

T1 - WNT-3a modulates platelet function by regulating small GTPase activity

AU - Steele, Brian M

AU - Harper, Matthew T

AU - Smolenski, Albert P

AU - Alkazemi, Naheda

AU - Poole, Alastair W

AU - Fitzgerald, Desmond J

AU - Maguire, Patricia B

PY - 2012/7/30

Y1 - 2012/7/30

N2 - Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.

AB - Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)β(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.

KW - Recombinant Proteins

KW - Humans

KW - Wnt3A Protein

KW - rap GTP-Binding Proteins

KW - Hydrolysis

KW - Models, Biological

KW - Guanosine Triphosphate

KW - Blood Platelets

KW - Adaptor Proteins, Signal Transducing

KW - Extracellular Matrix

KW - rac1 GTP-Binding Protein

KW - Gene Expression Regulation

KW - Monomeric GTP-Binding Proteins

KW - cdc42 GTP-Binding Protein

KW - Signal Transduction

KW - Densitometry

U2 - 10.1016/j.febslet.2012.05.060

DO - 10.1016/j.febslet.2012.05.060

M3 - Article (Academic Journal)

C2 - 22705156

SN - 1873-3468

VL - 586

SP - 2267

EP - 2272

JO - FEBS Letters

JF - FEBS Letters

IS - 16

ER -

WNT-3a modulates platelet function by regulating small GTPase activity

Abstract

Bibliographical note

Keywords

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