Cutting edge: A chemical genetic system for the analysis of kinases regulating T cell development
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Cutting edge: A chemical genetic system for the analysis of kinases regulating T cell development. / Denzel, A; Hare, Katherine; Zhang, C; Shokat, K; Jenkinson, EY; Anderson, Graham; Hayday, A.
In: Journal of Immunology, Vol. 171, No. 2, 01.07.2003, p. 519-523.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Cutting edge: A chemical genetic system for the analysis of kinases regulating T cell development
AU - Denzel, A
AU - Hare, Katherine
AU - Zhang, C
AU - Shokat, K
AU - Jenkinson, EY
AU - Anderson, Graham
AU - Hayday, A
PY - 2003/7/1
Y1 - 2003/7/1
N2 - To understand the regulatory activities of kinases in vivo requires their study across a biologically relevant window of activity. To this end, ATP analog-sensitive kinase alleles (ASKAs) specifically sensitive to a competitive inhibitor have been developed. This article tests whether ASKA technology can be applied to complex immunological systems, such as lymphoid development. The results show that when applied to reaggregate thymic organ culture, novel p56(Lck) ASKAs readily expose a dose-dependent correlation of thymocyte development with a range of p56(Lck) activity. By regulating kinase activity, rather than amounts of RNA or protein, ASKA technology offers a general means for assessing the quantitative contributions to immunology of numerous kinases emerging from genomics analyses. It can obviate the generation of multiple lines of mice expressing different levels of kinase transgenes and should permit specific biological effects to be associated with defined biochemical activities.
AB - To understand the regulatory activities of kinases in vivo requires their study across a biologically relevant window of activity. To this end, ATP analog-sensitive kinase alleles (ASKAs) specifically sensitive to a competitive inhibitor have been developed. This article tests whether ASKA technology can be applied to complex immunological systems, such as lymphoid development. The results show that when applied to reaggregate thymic organ culture, novel p56(Lck) ASKAs readily expose a dose-dependent correlation of thymocyte development with a range of p56(Lck) activity. By regulating kinase activity, rather than amounts of RNA or protein, ASKA technology offers a general means for assessing the quantitative contributions to immunology of numerous kinases emerging from genomics analyses. It can obviate the generation of multiple lines of mice expressing different levels of kinase transgenes and should permit specific biological effects to be associated with defined biochemical activities.
M3 - Article
C2 - 12847211
VL - 171
SP - 519
EP - 523
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -