roles of the src tyrosine kinases lck and fyn in regulating γδtcr signal strength角色的src酪氨酸激酶lck和菲英岛在调节γδtcr信号强度.pdfVIP

Roles of the Src Tyrosine Kinases Lck and Fyn in Regulating cdTCR Signal Strength Renee M. Laird, Sandra M. Hayes* Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, New York, United States of America Abstract Lck and Fyn, members of the Src family of tyrosine kinases, are key components of the abTCR-coupled signaling pathway. While it is generally accepted that both Lck and Fyn positively regulate signal transduction by the abTCR, recent studies have shown that Lck and Fyn have distinct functions in this signaling pathway, with Lck being a positive regulator and Fyn being a negative regulator of abTCR signal transduction. To determine whether Lck and Fyn also differentially regulate cdTCR signal transduction, we analyzed cd T cell development and function in mice with reduced Lck or Fyn expression levels. We found that reducing Lck or Fyn levels altered the strength of the cdTCR signaling response, with low levels of Lck weakening cdTCR signal strength and low levels of Fyn augmenting cdTCR signal strength. These alterations in cdTCR signal strength had profound effects not only on ab/cd lineage choice, but also on cd thymocyte maturation and cd T cell effector function. These results indicate that the cellular levels of Lck and Fyn play a role in regulating the strength of the cdTCR signaling response at different stages in the life of the cd T cell. Citation: Laird RM, Hayes SM (2010) Roles of the Src Tyrosine Kinases Lck and Fyn in Regulating cdTCR Signal Strength. PLoS ONE 5(1): e8899. doi:10.1371/ journal.pone.0008899 Editor: Jose Alberola-Ila, Oklahoma Medical Research Foundation, United States of America Received November 27, 2009; Accepted January 6, 2010; Published January 26, 2010 Copyright: 2010 Laird, Hayes. This is an open-access article distributed under the terms of the Creative Commons A