Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane

The PKB (protein kinase B, also called Akt) family of protein kinases plays a key role in insulin signaling, cellular survival, and transformation. PK B is activated by phosphorylation on residues threonine 308, by the protein kinase PDK1, and Serine 473, by a putative serine 473 kinase. Several prot ein binding partners for PKB have been identified. Here, we describe a prot ein partner for PKB alpha termed CTMP, or carboxyl-terminal modulator prote in, that binds specifically to the carboxyl-terminal regulatory domain of P KB alpha at the plasma membrane. Binding of CTMP reduces the activity of PK B alpha by inhibiting phosphorylation on serine 473 and threonine 308. More over, CTMP expression reverts the phenotype of v-Akt-transformed cells exam ined under a number of criteria including cell morphology, growth rate, and in vivo tumorigenesis. These findings identify CTMP as a negative regulato ry component of the pathway controlling PKB activity.