OSBP-Related Protein 5L Maintains Intracellular IP3/Ca2+ Signaling and Proliferation in T Cells by Facilitating PIP2 Hydrolysis.
J Immunol
; 204(5): 1134-1145, 2020 03 01.
Article
em En
| MEDLINE
| ID: mdl-31953353
ABSTRACT
Phospholipase C (PLC) isoforms play central roles in signaling cascades by cleaving PIP2 into the second messengers IP3 and DAG. In this study, to our knowledge, we uncover that ORP5L interacts physically with PLCγ1 in T cells, extracts PIP2 from the plasma membrane via its ORD domain (OSBP-related domain), presents it to PLCγ1 (enabling IP3 generation), and eventually maintains intracellular Ca2+ homeostasis. Through this mechanism, ORP5L promotes T cell proliferation in a Ca2+-activated NFAT2-dependent manner. To our knowledge, our study uncovers a new key function of ORP5L as a critical cofactor for PLCγ1 catalysis and its crucial role in human T cell proliferation.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Esteroides
/
Inositol 1,4,5-Trifosfato
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Fosfatidilinositol 4,5-Difosfato
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Sinalização do Cálcio
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Proliferação de Células
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article