Identification of a plasma membrane raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1

Hill, Michelle M., Feng, Jianhua and Hemmings, Brian A. (2002) Identification of a plasma membrane raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1. Current Biology, 12 14: 1251-1255. doi:10.1016/S0960-9822(02)00973-9


Author Hill, Michelle M.
Feng, Jianhua
Hemmings, Brian A.
Title Identification of a plasma membrane raft-associated PKB Ser473 kinase activity that is distinct from ILK and PDK1
Journal name Current Biology   Check publisher's open access policy
ISSN 0960-9822
Publication date 2002-07
Sub-type Article (original research)
DOI 10.1016/S0960-9822(02)00973-9
Volume 12
Issue 14
Start page 1251
End page 1255
Total pages 5
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract Protein kinase B (PKB/Akt) has been well established as an important signaling intermediate, and its deregulation has been implicated in the development of human cancer and diabetes (reviewed in [1]). Full activation of PKB requires phosphorylation on residues Thr308 and Ser473 [2]. While the Thr308 kinase, named 3-phosphoinositide-dependent kinase-1 (PDK1), has been extensively characterized (reviewed in [3]), the identity of the Ser473 kinase remains unclear. We have focused our study on the plasma membrane (PM) fraction because membrane localization is sufficient to activate PKB [4], [5], [6] and [7], and this suggests that PKB upstream kinases are constitutively active at the membrane. Here, we report the identification of a constitutively active PKB Ser473 kinase activity enriched in buoyant, detergent-insoluble plasma membrane rafts that are distinct from the cytosolic distribution of PKB and PDK1. This Ser473 kinase activity was released from the membrane by high salt, and gel filtration analysis showed that the kinase responsible is present in a large complex of >500 kDa. Two major phosphoproteins and integrin-linked kinase (ILK) were detected in partially purified PKB Ser473 kinase preparations. In contrast to previous observations, however, ILK immunoprecipitates did not retain Ser473 kinase activity. Thus, we have identified a novel raft-associated PKB Ser473 kinase, implicating a role for lipid rafts in PKB signaling.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Mon, 20 Dec 2010, 13:45:37 EST