A reevaluation of the spleen tyrosine kinase (SYK) activation mechanism.

ITAM (immune-receptor tyrosine activation motif) autophosphorylation cell signaling conformational change enzyme activation enzyme kinetics immunity non-receptor tyrosine kinase (nRTK) phosphorylation spleen tyrosine kinase (SYK) tonic signalling

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
10 05 2019
Historique:
received: 15 02 2019
revised: 25 03 2019
pubmed: 30 3 2019
medline: 18 12 2019
entrez: 30 3 2019
Statut: ppublish

Résumé

Spleen tyrosine kinase (SYK) is a signaling node in many immune pathways and comprises two tandem Src homology (SH) 2 domains, an SH2-kinase linker, and a C-terminal tyrosine kinase domain. Two prevalent models of SYK activation exist. The "OR-gate" model contends that SYK can be fully activated by phosphorylation or binding of its SH2 domains to a dual-phosphorylated immune-receptor tyrosine-based activation motif (ppITAM). An alternative model proposes that SYK activation requires ppITAM binding and phosphorylation of the SH2-kinase linker by a SRC family kinase such as LYN proto-oncogene, SRC family tyrosine kinase (LYN). To evaluate these two models, we generated directly comparable unphosphorylated (upSYK) and phosphorylated (pSYK) proteins with or without an N-terminal glutathione

Identifiants

pubmed: 30923129
pii: S0021-9258(20)35462-4
doi: 10.1074/jbc.RA119.008045
pmc: PMC6514621
doi:

Substances chimiques

MAS1 protein, human 0
Proto-Oncogene Mas 0
SYK protein, human EC 2.7.10.2
Syk Kinase EC 2.7.10.2
lyn protein-tyrosine kinase EC 2.7.10.2
src-Family Kinases EC 2.7.10.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7658-7668

Informations de copyright

© 2019 Mansueto et al.

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Auteurs

My S Mansueto (MS)

From the Departments of Pharmacology and.

Abigail Reens (A)

From the Departments of Pharmacology and.

Larissa Rakhilina (L)

From the Departments of Pharmacology and.

An Chi (A)

Chemical Biology, Merck & Co., Inc., Boston, Massachusetts 02115.

Bo-Sheng Pan (BS)

From the Departments of Pharmacology and.

J Richard Miller (JR)

From the Departments of Pharmacology and james.miller2@merck.com.

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Classifications MeSH