Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.

Engagement of the receptor CD244 (2B4) by its ligand CD48 has inhibitory and activating potential, and this differs depending on experimental systems in mouse and human. We show that, in both mouse and human upon engagement of its ligand CD48, CD244 can give a negative signal to natural killer cells...

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Hoofdauteurs: Clarkson, N, Simmonds, S, Puklavec, M, Brown, M
Formaat: Journal article
Taal:English
Gepubliceerd in: 2007
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author Clarkson, N
Simmonds, S
Puklavec, M
Brown, M
author_facet Clarkson, N
Simmonds, S
Puklavec, M
Brown, M
author_sort Clarkson, N
collection OXFORD
description Engagement of the receptor CD244 (2B4) by its ligand CD48 has inhibitory and activating potential, and this differs depending on experimental systems in mouse and human. We show that, in both mouse and human upon engagement of its ligand CD48, CD244 can give a negative signal to natural killer cells, implying conservation of function between the two species. The signaling mechanisms used by CD244 in both human and mouse are conserved as shown by quantitative analyses of the direct molecular interactions of the SH2 domains of the adaptors SLAM-associated protein (SAP) and EAT-2 and of FYN kinase with CD244 together with the indirect interactions of the FYN SH2 domain with EAT-2. Functional experiments support the biochemical hierarchy of interactions and show that EAT-2 is not inhibitory per se. The data are consistent with a model in which the mechanism of signal transduction by CD244 is to regulate FYN kinase recruitment and/or activity and the outcome of CD48/CD244 interactions is determined by which other receptors are engaged.
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spelling oxford-uuid:573304e5-52f5-4332-bf95-719a69e6b4e22022-03-26T16:55:16ZDirect and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:573304e5-52f5-4332-bf95-719a69e6b4e2EnglishSymplectic Elements at Oxford2007Clarkson, NSimmonds, SPuklavec, MBrown, MEngagement of the receptor CD244 (2B4) by its ligand CD48 has inhibitory and activating potential, and this differs depending on experimental systems in mouse and human. We show that, in both mouse and human upon engagement of its ligand CD48, CD244 can give a negative signal to natural killer cells, implying conservation of function between the two species. The signaling mechanisms used by CD244 in both human and mouse are conserved as shown by quantitative analyses of the direct molecular interactions of the SH2 domains of the adaptors SLAM-associated protein (SAP) and EAT-2 and of FYN kinase with CD244 together with the indirect interactions of the FYN SH2 domain with EAT-2. Functional experiments support the biochemical hierarchy of interactions and show that EAT-2 is not inhibitory per se. The data are consistent with a model in which the mechanism of signal transduction by CD244 is to regulate FYN kinase recruitment and/or activity and the outcome of CD48/CD244 interactions is determined by which other receptors are engaged.
spellingShingle Clarkson, N
Simmonds, S
Puklavec, M
Brown, M
Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title_full Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title_fullStr Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title_full_unstemmed Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title_short Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase.
title_sort direct and indirect interactions of the cytoplasmic region of cd244 2b4 in mice and humans with fyn kinase
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