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 prompt clearance of cells undergoing apoptosis is critical during embryonic development and normal tissue turnover, as well as during inflammation and autoimmune responses. We recently demonstrated that
stabilin-2
is a phosphatidylserine receptor that mediates the clearance of apoptotic cells, thereby releasing the anti-inflammatory cytokine, transforming growth factor-beta. However, the downstream signaling components of
stabilin-2
-mediated phagocytosis are not known. Here, we provide evidence that the adaptor protein, GULP, physically and functionally interacts with the
stabilin-2
cytoplasmic tail. Using fluorescent resonance energy transfer analysis and biochemical approaches, we show that GULP directly binds to the cytoplasmic tail of
stabilin-2
. Knockdown of endogenous GULP expression significantly decreased
stabilin-2
-mediated phagocytosis. Conversely, overexpression of GULP caused an increase in aged cell engulfment. The phosphotyrosine binding (PTB) domain of GULP was sufficient for the interaction with
stabilin-2
; therefore, transduction of
TAT
fusion PTB domain acts as a dominant negative, resulting in impaired engulfment of aged red blood cells in
stabilin-2
expressing cells. In addition, the PTB domain of GULP was able to specifically interact with the NPXY motif of the
stabilin-2
cytoplasmic tail. Taken together, these results indicate that GULP is a likely downstream molecule in the
stabilin-2
-mediated signaling pathway and plays an important role in
stabilin-2
-mediated phagocytosis.
...
PMID:Requirement of adaptor protein GULP during stabilin-2-mediated cell corpse engulfment. 1823 Jun 8
