Linked Life Data

17056523

Source:http://linkedlifedata.com/resource/pubmed/id/17056523

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-10-23
pubmed:abstractText
It is well known that T cell differentiation and maturation in the thymus is tightly controlled at multiple checkpoints. However, the molecular mechanism for the control of this developmental program is not fully understood. A number of protein tyrosine kinases, such as Zap-70, Lck, and Fyn, have been shown to promote signals required for thymocyte development, whereas a tyrosine phosphatase Src homology domain-containing tyrosine phosphatase (Shp)1 has a negative effect in pre-TCR and TCR signaling. We show in this study that Shp2, a close relative of Shp1, plays a positive role in T cell development and functions. Lck-Cre-mediated deletion of Shp2 in the thymus resulted in a significant block in thymocyte differentiation/proliferation instructed by the pre-TCR at the beta selection step, and reduced expansion of CD4(+) T cells. Furthermore, mature Shp2(-/-) T cells showed decreased TCR signaling in vitro. Mechanistically, Shp2 acts to promote TCR signaling through the ERK pathway, with impaired activation of ERK kinase observed in Shp2(-/-) T cells. Thus, our results provide physiological evidence that Shp2 is a common signal transducer for pre-TCR and TCR in promoting T cell maturation and proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
177
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5990-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17056523-Animals, pubmed-meshheading:17056523-Cell Differentiation, pubmed-meshheading:17056523-Cell Proliferation, pubmed-meshheading:17056523-Enzyme Activation, pubmed-meshheading:17056523-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:17056523-Gene Deletion, pubmed-meshheading:17056523-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17056523-Lymphocyte Count, pubmed-meshheading:17056523-Mice, pubmed-meshheading:17056523-Mice, Knockout, pubmed-meshheading:17056523-Protein Tyrosine Phosphatase, Non-Receptor Type 11, pubmed-meshheading:17056523-Protein Tyrosine Phosphatases, pubmed-meshheading:17056523-Receptors, Antigen, T-Cell, pubmed-meshheading:17056523-Signal Transduction, pubmed-meshheading:17056523-Spleen, pubmed-meshheading:17056523-T-Lymphocytes, pubmed-meshheading:17056523-Thymus Gland
pubmed:year
2006
pubmed:articleTitle
Conditional deletion of Shp2 tyrosine phosphatase in thymocytes suppresses both pre-TCR and TCR signals.
pubmed:affiliation
Programs in Signal Transduction and Stem Cells and Regeneration, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural