First Author | Kumar L | Year | 2005 |
Journal | Proc Natl Acad Sci U S A | Volume | 102 |
Issue | 52 | Pages | 19063-8 |
PubMed ID | 16354835 | Mgi Jnum | J:104696 |
Mgi Id | MGI:3612639 | Doi | 10.1073/pnas.0509176102 |
Citation | Kumar L, et al. (2005) A 10-aa-long sequence in SLP-76 upstream of the Gads binding site is essential for T cell development and function. Proc Natl Acad Sci U S A 102(52):19063-8 |
abstractText | The adapter SLP-76 is essential for T cell development and function. SLP-76 binds to the src homology 3 domain of Lck in vitro. This interaction depends on amino acids 185-194 of SLP-76. To examine the role of the Lck-binding region of SLP-76 in T cell development and function, SLP-76(-/-) mice were reconstituted with an SLP-76 mutant that lacks amino acids 185-194. Double and single positive thymocytes from reconstituted mice were severely reduced in numbers and exhibited impaired positive selection and increased apoptosis. Peripheral T cells were also reduced in numbers, exhibited impaired phospholipase C-gamma1 and Erk phosphorylation, and failed to flux calcium, secrete IL-2, and proliferate in response to T cell antigen receptor ligation. Delayed cutaneous hypersensitivity responses and Ab responses to T cell-dependent antigen were severely impaired. These results indicate that the Lck binding region of SLP-76 is essential for T cell antigen receptor signaling and normal T cell development and function. |