Editors' ChoiceKinase Inhibition

Regulating Protein Kinase B

Science's STKE  16 Oct 2001:
Vol. 2001, Issue 104, pp. tw377
DOI: 10.1126/stke.2001.104.tw377

Protein kinase B (PKB) has proven to be a key regulatory element in growth factor signaling, cell survival, and transformation to a cancerous phenotype. Maira et al. screened for proteins that physically interacted with PKB and identified a human protein, which they call carboxyl-terminal modulator protein (CTMP), that binds to PKB at the plasma membrane and inhibits activation of the kinase. Inhibition of CTMP expression enhanced activation of PKB, whereas cells expressing a viral homolog of PKB became transformed and proliferated abnormally and could form tumors in vivo. However, clones of such cells stably expressing CTMP grew more slowly and either failed to form tumors in vivo or formed tumors that grew more slowly. Thus, CTMP appears to be an important regulator of PKB, an enzyme with critical roles from insulin signaling to protection of cells from apoptosis.

S.-M. Maira, I. Galetic, D. P. Brazil, S. Kaech, E. Ingley, M. Thelen, B. A. Hemmings, Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science 294 374-380 (2001). [Abstract] [Full Text]