The Ras/MAPK cascade and the control of positive selection
Immature double positive (DP) thymocytes bearing a T cell receptor (TCR) that interacts with self‐major histocompatibility complex (MHC) molecules receive signals that induce either their differentiation (positive selection) or apoptosis (negative selection). Furthermore, those cells that are positi...
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Published in | Immunological reviews Vol. 191; no. 1; pp. 79 - 96 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Munksgaard International Publishers
01.02.2003
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | Immature double positive (DP) thymocytes bearing a T cell receptor (TCR) that interacts with self‐major histocompatibility complex (MHC) molecules receive signals that induce either their differentiation (positive selection) or apoptosis (negative selection). Furthermore, those cells that are positively selected develop into two different lineages, CD4 or CD8, depending on whether their TCRs bind to MHC class II or I, respectively. Positive selection therefore involves rescue from the default fate (death), lineage commitment, and progression to the single positive (SP) stage. These are probably temporally distinct events that may require both unique and overlapping signals. Work in the past several years has started to unravel the signaling networks that control these processes. One of the first pathways identified as important for positive selection was Ras and its downstream effector, the Erk mitogen‐activated protein kinase (MAPK) cascade. In this review we examine the factors that connect the TCR to the Ras/Erk cascade in DP thymocytes, as well as what we know about the downstream effectors of the Ras/Erk cascade important for positive selection. We also consider the possible role of this cascade in CD4/CD8 lineage development, and the possible interactions of the Ras/Erk cascade with Notch during these cell fate determination processes. |
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Bibliography: | istex:CFBFD3D56FDAA4D432EACA557A55A9CAE5C6ACEC ArticleID:IMR012 ark:/67375/WNG-QFH2CRQZ-Q ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Feature-3 ObjectType-Review-1 |
ISSN: | 0105-2896 1600-065X |
DOI: | 10.1034/j.1600-065X.2003.00012.x |