A novel regulatory mechanism links PLCγ1 to PDK1.

Abstract:

:3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C (PLC)γ1 are two key enzymes in signal transduction that control several intracellular processes. Despite the fact that PLCγ1 has been investigated for several years, the mechanisms of activation of this enzyme are still not completely clear. Similarly, although PDK1 has been mostly investigated for its role in activation of Akt, a crucial enzyme in regulation of several cellular processes, it has become evident recently that the role of PDK1 in physiological and pathological conditions is not limited to Akt activation. Here we demonstrate that PDK1 regulates PLCγ1 activation in a mechanism involving association of the two enzymes and modulation of PLCγ1 tyrosine phosphorylation. We further show that this novel PDK1-PLCγ1 pathway is important for cancer cell invasion. The identification of a PDK1-PLCγ1 pathway reveals the existence of a previously undetected link between two of the most important enzymes in signal transduction. This is likely to have profound consequences for our understanding of several cellular functions that are dependent on phosphoinositides and controlled by PDK1 and PLCγ1.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Raimondi C,Chikh A,Wheeler AP,Maffucci T,Falasca M

doi

10.1242/jcs.100511

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

3153-63

issue

Pt 13

eissn

0021-9533

issn

1477-9137

pii

jcs.100511

journal_volume

125

pub_type

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