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A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling

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Pandey, A Ibarrola, N Kratchmarova, I Fernandez, MM Constantinescu, Stefan N. [UCL] Mann, M

We have cloned a novel adapter protein containing Src homology 2 and Src homology 3 domains similar to the Src family of tyrosine kinases. This molecule lacks a catalytic tyrosine kinase domain and is related to a previously identified protein, Src-like adapter protein (SLAP), and is therefore designated SLAP-2. Northern blot analysis indicates that SLAP-2 is predominantly expressed in the immune system. Jurkat, T cells express SLAP-2 protein and overexpression of SLAP-2 in these cells negatively regulates T cell receptor signaling as assessed by interleukin-2 promoter or NF-AT promoter reporter constructs. Mutational analysis revealed that an intact SH2 domain of SLAP-2 is essential for this inhibitory effect, whereas mutation of the SH3 domain alone has no effect. This inhibitory effect is upstream of the activation of Ras and increase of intracellular calcium levels, as no inhibition was observed when the cells were activated by phorbol ester plus ionomycin. SLAP-2 interacts with Cbl in vivo in a phosphorylation independent manner and with ZAP-70 and T cell receptor chain upon T cell receptor activation. Finally, we show that the mutation of a predicted myristoylation site within the NH2-terminal of SLAP-2 is essential for its inhibitory effect. This report therefore implicates SLAP and SLAP-2 as a family of adapter proteins that negatively regulate T cell receptor signaling.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2002
Language Anglais
Journal information "Journal of Biological Chemistry" - Vol. 277, no. 21, p. 19131-19138 (2002)
Peer reviewed yes
Publisher Amer Soc Biochemistry Molecular Biology Inc (Bethesda)
issn 0021-9258
e-issn 1083-351X
Publication status Publié
Affiliation UCL
Links
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Bibliographic reference Pandey, A ; Ibarrola, N ; Kratchmarova, I ; Fernandez, MM ; Constantinescu, Stefan N. ; et. al. A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling. In: Journal of Biological Chemistry, Vol. 277, no. 21, p. 19131-19138 (2002)
Permanent URL http://hdl.handle.net/2078.1/41903