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Science 12 October 2001:
Vol. 294. no. 5541, pp. 374 - 380
DOI: 10.1126/science.1062030
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Reports

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,1dagger Marcus Thelen,2 Brian A. Hemmings1ddagger

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 PKBalpha termed CTMP, or carboxyl-terminal modulator protein, that binds specifically to the carboxyl-terminal regulatory domain of PKBalpha at the plasma membrane. Binding of CTMP reduces the activity of PKBalpha 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.

dagger    Present address: Department of Biochemistry, Royal Perth Hospital, GPO Box X2213, Western Australia 6001, Australia.

ddagger    To whom correspondence should be addressed. E-mail: hemmings{at}fmi.ch

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