Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic

K Sakamoto, Geoffrey D Holman

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

Vesicular traffic of the glucose transporter GLUT4 occurs in response to insulin, muscle contraction, and metabolic stimuli that lead to changes in the energy status of the cell. These stimuli are associated with linked kinase cascades that lead to changes in glucose uptake that meet the energy challenges imposed on the highly regulated cell types in insulin-responsive tissues. The need to mechanistically link these kinase-associated stimuli to identifiable intermediates in vesicular traffic has long been known but has been difficult to fulfill. The Rab-GTPase-activating proteins AS160 and TBC1D1 have now emerged as strong candidates to fill this void. Here we review the initial discovery of these proteins as phosphorylated substrates for Akt and the more recent emerging data that indicate that these proteins are substrates for additional kinases that are downstream of contraction and energy status signaling. The mechanism of coupling these phosphorylated proteins to vesicle traffic appears to be dependent on linking to small GTPase of the Rab family. We examine the current state of a hypothesis that suggests that phosphorylation of the Rab-GTPase-activating proteins leads to increased GTP loading of Rab proteins on GLUT4 vesicles and subsequently to increased interaction with Rab effectors that control GLUT4 vesicle translocation.
Original languageEnglish
Pages (from-to)E29-E37
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume295
Issue number1
DOIs
Publication statusPublished - 1 Jul 2008

Fingerprint

rab GTP-Binding Proteins
GTPase-Activating Proteins
Phosphotransferases
Glucose Transporter Type 4
Insulin
Proteins
Monomeric GTP-Binding Proteins
Facilitative Glucose Transport Proteins
Muscle Contraction
Guanosine Triphosphate
Phosphorylation
Glucose

Cite this

Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic. / Sakamoto, K; Holman, Geoffrey D.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 295, No. 1, 01.07.2008, p. E29-E37.

Research output: Contribution to journalArticle

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