MIST functions through distinct domains in immunoreceptor signaling in thepresence and absence of LAT

Citation
R. Goitsuka et al., MIST functions through distinct domains in immunoreceptor signaling in thepresence and absence of LAT, J BIOL CHEM, 276(38), 2001, pp. 36043-36050
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
38
Year of publication
2001
Pages
36043 - 36050
Database
ISI
SICI code
0021-9258(20010921)276:38<36043:MFTDDI>2.0.ZU;2-G
Abstract
MIST (also termed Clnk) is an adaptor protein structurally related to SLP-7 6 and BLNY./BASWSLP-65 hematopoietic cell-specific adaptor proteins. By usi ng the BLNK-deficient DT40 chicken B cell system, we demonstrated MIST func tions through distinct intramolecular domains in immunoreceptor signaling d epending on the availability of linker for activation of T cells (LAT). MIS T can partially restore the B cell antigen receptor (BCR) signaling in the BLNK-deficient cells, which requires phosphorylation of the two N-terminal tyrosine residues. Co-expression of LAT with MIST fully restored the BCR si gnaling and dispenses with the requirement of the two tyrosines in MIST for BCR signaling. However, some other tyrosine(s), as well as the Src homolog y (SH) 2 domain and the two proline-rich regions in MIST is still required for full reconstitution of the BCR signaling, in cooperation with LAT. The C-terminal proline-rich region of MIST is dispensable for the LAT-aided ful l restoration of MAP kinase activation, although it is responsible for the interaction with LAT and for the localization in glycolipid-enriched microd omains. On the other hand, the N-terminal proline-rich region, which is a b inding site of the SH3 domain of phospholipase Cy, is essential for BCR sig naling. These results revealed a marked plasticity of MIST function as an a daptor in the cell contexts with or without LAT.