Datasheet

生物学的記述

Specificity	TBC1D1 Antibody [C20L8] detects endogenous levels of total TBC1D1 protein.
Background	TBC1D1 is a Rab-GTPase activating protein (Rab-GAP) enriched in skeletal muscle and closely related to AS160/TBC1D4. It serves as a key metabolic sensor coordinating glucose uptake in response to both insulin and muscle contraction by regulating GLUT4 vesicle trafficking. Insulin activates Akt, leading to phosphorylation of TBC1D1 at Thr590, which relieves Rab10 and Rab14 inhibition and enables GLUT4 exocytosis. In contrast, muscle contraction or AICAR activates AMPK, phosphorylating Ser231, Ser660, and Ser700, promoting 14-3-3 protein binding, further disinhibiting Rab-GAP activity and enhancing GLUT4 translocation independently of Akt. Contraction increases AMPK site phosphorylation, while insulin selectively targets Thr590 via Akt2. AMPKα2 inactivation significantly reduces contraction-stimulated phosphorylation at these sites, highlighting AMPK’s dominant role during exercise. This dual regulation converges on Rab10 inactivation. Phospho-null TBC1D1 mutants accelerate contraction-stimulated GLUT4 translocation, while TBC1D1 overexpression impairs insulin sensitivity. TBC1D1 is crucial for metabolic flexibility in skeletal muscle during fasting, exercise, and feeding, and is a major target for research using transgenic models or phospho-site specific antibodies, especially in studies of exercise-mimetic drugs. Loss-of-function mutations in TBC1D1 cause severe obesity and insulin resistance, and its phosphorylation pattern remains intact with high-fat diet-induced insulin resistance, underscoring its role in exercise signaling.

Specificity

TBC1D1 Antibody [C20L8] detects endogenous levels of total TBC1D1 protein.

Background

TBC1D1 is a Rab-GTPase activating protein (Rab-GAP) enriched in skeletal muscle and closely related to AS160/TBC1D4. It serves as a key metabolic sensor coordinating glucose uptake in response to both insulin and muscle contraction by regulating GLUT4 vesicle trafficking. Insulin activates Akt, leading to phosphorylation of TBC1D1 at Thr590, which relieves Rab10 and Rab14 inhibition and enables GLUT4 exocytosis. In contrast, muscle contraction or AICAR activates AMPK, phosphorylating Ser231, Ser660, and Ser700, promoting 14-3-3 protein binding, further disinhibiting Rab-GAP activity and enhancing GLUT4 translocation independently of Akt. Contraction increases AMPK site phosphorylation, while insulin selectively targets Thr590 via Akt2. AMPKα2 inactivation significantly reduces contraction-stimulated phosphorylation at these sites, highlighting AMPK’s dominant role during exercise. This dual regulation converges on Rab10 inactivation. Phospho-null TBC1D1 mutants accelerate contraction-stimulated GLUT4 translocation, while TBC1D1 overexpression impairs insulin sensitivity. TBC1D1 is crucial for metabolic flexibility in skeletal muscle during fasting, exercise, and feeding, and is a major target for research using transgenic models or phospho-site specific antibodies, especially in studies of exercise-mimetic drugs. Loss-of-function mutations in TBC1D1 cause severe obesity and insulin resistance, and its phosphorylation pattern remains intact with high-fat diet-induced insulin resistance, underscoring its role in exercise signaling.

使用情報

Application

WB, IP

Dilution

WB	IP
1:1000	1:50

Reactivity

Mouse

Source

Rabbit Monoclonal Antibody

MW

160 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

プロトコール

References

https://pubmed.ncbi.nlm.nih.gov/20701589/
https://pubmed.ncbi.nlm.nih.gov/18276596/

Application Data

WB

Validated by Selleck

Lane 1: C2C12