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Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization.

ABSTRACT: CD36 is a versatile receptor known to play a central role in the development of atherosclerosis, the pathogenesis of malaria, and the removal of apoptotic cells. Remarkably, the short cytosolically exposed regions of CD36 lack identifiable motifs, which has hampered elucidation of its mode of signaling. Using a combination of phosphoprotein isolation, mass spectrometry, superresolution imaging, and gene silencing, we have determined that the receptor induces ligand internalization through a heteromeric complex consisting of CD36, ?1 and/or ?2 integrins, and the tetraspanins CD9 and/or CD81. This receptor complex serves to link CD36 to the adaptor FcR?, which bears an immunoreceptor tyrosine activation motif. By coupling to FcR?, CD36 is able to engage Src-family kinases and Syk, which in turn drives the internalization of CD36 and its bound ligands.

SUBMITTER: Heit B

PROVIDER: S-EPMC3586299 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Multimolecular signaling complexes enable Syk-mediated signaling of CD36 internalization.

Heit Bryan B Kim Hani H Cosío Gabriela G Castaño Diana D Collins Richard R Lowell Clifford A CA Kain Kevin C KC Trimble William S WS Grinstein Sergio S

Developmental cell 20130207 4

CD36 is a versatile receptor known to play a central role in the development of atherosclerosis, the pathogenesis of malaria, and the removal of apoptotic cells. Remarkably, the short cytosolically exposed regions of CD36 lack identifiable motifs, which has hampered elucidation of its mode of signaling. Using a combination of phosphoprotein isolation, mass spectrometry, superresolution imaging, and gene silencing, we have determined that the receptor induces ligand internalization through a hete ...[more]

PMID: 23395392

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