Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.1.108 (
TAT
)
2,389
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The human granulocyte-specific receptor carcinoembryonic antigen-related cell adhesion molecule (CEACAM)3 is critically involved in the opsonin-independent recognition of several bacterial pathogens.
CEACAM3
-mediated phagocytosis depends on the integrity of an ITAM-like sequence within the cytoplasmic domain of
CEACAM3
and is characterized by rapid stimulation of the GTPase Rac. By performing a functional screen with
CEACAM3
-expressing cells, we found that overexpression of a dominant-negative form of the guanine nucleotide exchange factor Vav, but not the dominant-negative versions SWAP70, Dock2, or ELMO1 interfered with
CEACAM3
-initiated phagocytosis. Moreover, small interfering RNA-mediated silencing of Vav reduced uptake and abrogated the stimulation of Rac in response to bacterial
CEACAM3
engagement. In Vav1/Vav2-deficient cells,
CEACAM3
-mediated internalization was only observed after re-expression of Vav. Vav colocalized with
CEACAM3
upon bacterial infection, coimmunoprecipitated in a complex with
CEACAM3
, and the Vav Src homology 2 domain directly associated with phosphorylated Tyr(230) of
CEACAM3
. In primary human granulocytes,
TAT
-mediated transduction of dominant-negative Vav, but not SWAP70, severely impaired the uptake of
CEACAM3
-binding bacteria. These data support the view that, different from canonical ITAM signaling, the
CEACAM3
ITAM-like sequence short-wires bacterial recognition and Rac stimulation via a direct association with Vav to promote rapid phagocytosis and elimination of CEACAM-binding human pathogens.
...
PMID:The granulocyte receptor carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) directly associates with Vav to promote phagocytosis of human pathogens. 1733 78
