Carboxyl-Terminal Modulator Protein (CTMP), a Negative Regulator of PKB/Akt and v-Akt at the Plasma Membrane
Sauveur-Michel Maira,1
Ivana Galetic,1
Derek P. Brazil,1
Stefanie Kaech,1*
Evan Ingley,1
Marcus Thelen,2
Brian A. Hemmings1
The PKB (protein kinase B, also called Akt) family of
protein kinases plays a key role in insulin signaling, cellular
survival, and transformation. PKB is activated by
phosphorylation on residues threonine 308, by the protein
kinase PDK1, and Serine 473, by a putative serine 473 kinase. Several
protein binding partners for PKB have been identified. Here, we
describe a protein partner for PKB
termed CTMP, or carboxyl-terminal
modulator protein, that binds specifically to the carboxyl-terminal
regulatory domain of PKB at the plasma membrane. Binding of CTMP
reduces the activity of PKB by inhibiting
phosphorylation on serine 473 and threonine 308. Moreover,
CTMP expression reverts the phenotype of v-Akt-transformed cells examined under a number of criteria including cell morphology, growth rate, and in vivo tumorigenesis. These findings identify CTMP as
a negative regulatory component of the pathway controlling PKB
activity.
1 Friedrich Miescher Institute, Post Office Box
2543, CH-4002 Basel, Switzerland.
2 Institute for
Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
*
Present address: Center for Research in Occupational and
Environmental Toxicology, Oregon Health Science University, Portland, OR 97201-3098, USA.
Present address: Department of Biochemistry, Royal
Perth Hospital, GPO Box X2213, Western Australia 6001, Australia.
To whom correspondence should be addressed. E-mail:
hemmings{at}fmi.ch
