Linked Life Data

20851766

Source:http://linkedlifedata.com/resource/pubmed/id/20851766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-10-18
pubmed:abstractText
Pre-T-cell receptor (pre-TCR) and TCR signals govern the development of T-lymphocytes. RhoH, a hematopoietic-specific and GTPase-deficient member of the RhoGTPase family, is required in the development of T-lymphocytes. Here we found that RhoH binds and modulates LCK, the non-receptor tyrosine kinase crucial in initiating pre-TCR and TCR signallings. In both pre-TCR and TCR signalling transduction, LCK is phosphorylated by CSK to maintain the inactive state of LCK at rest. Upon being activated, CSK phosphorylation is removed and LCK autophosphorylation leads to LCK activation and further phosphorylates ZAP70 to initiate further downstream signalling. At rest, LCK may be recruited to the plasma membrane by RhoH, which also binds CSK, resulting in LCK inactivation. Additionally, the presence of RhoH enhances the inactivation phosphorylation of LCK by CSK. RhoH was found to bind preferentially inactive LCK, indicating that, upon ligand-mediated TCR activation, LCK is dephosphorylated resulting in LCK autoactivation and its release from RhoH. Thus RhoH is a critical part of the microenvironment for maintaining the inactive state of LCK. Furthermore, we found that the reduction of RhoH levels results in LCK autoactivation and constitutive activation of the TCR pathway. Our findings indicate that RhoH is a key adapter protein that maintains LCK in the inactive state, contributing to the regulation of both pre-TCR and TCR signalling during T-cell development. The data also supports a model for ligand-independent signal transduction by pre-TCR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-3913
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-58
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
RhoH modulates pre-TCR and TCR signalling by regulating LCK.
pubmed:affiliation
Division of Hematology and Oncology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. howang@rci.rutgers.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural