Asset Details
Do you wish to reserve the book?
Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
Do you wish to request the book?
Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia
2001
Overview
The Wiskott-Aldrich syndrome protein (WASP; encoded by the gene
WAS
) and its homologs are important regulators of the actin cytoskeleton, mediating communication between Rho-family GTPases and the actin nucleation/crosslinking factor, the Arp2/3 complex
1
. Many
WAS
mutations impair cytoskeletal control in hematopoietic tissues, resulting in functional and developmental defects that define the X-linked Wiskott-Aldrich syndrome (WAS) and the related X-linked thrombocytopenia
2
(XLT). These diseases seem to result from reduced WASP signaling, often through decreased transcription or translation of the gene
3
,
4
,
5
,
6
,
7
,
8
. Here we describe a new disease, X-linked severe congenital neutropenia (XLN), caused by a novel L270P mutation in the region of
WAS
encoding the conserved GTPase binding domain (GBD).
In vitro
, the mutant protein is constitutively activated through disruption of an autoinhibitory domain in the wild-type protein, indicating that loss of WASP autoinhibition is a key event in XLN. Our findings highlight the importance of precise regulation of WASP in hematopoietic development and function, as impairment versus enhancement of its activity give rise to distinct spectra of cellular defects and clinical phenotypes.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Complications and side effects
/ Female
/ Females
/ Hematologic and hematopoietic diseases
/ Humans
/ letter
/ Male
/ Males
/ Mutation
/ Other diseases. Hematologic involvement in other diseases
/ Pedigree
/ Proteins
/ WAS gene
/ Wiskott-Aldrich Syndrome - genetics
