title: Molecular imaging of Akt kinase activity.
abstract: The serine/threonine kinase Akt mediates mitogenic and anti-apoptotic responses that result from activation of multiple signaling cascades. It is considered a key determinant of tumor aggressiveness and is a major target for anticancer drug development. Here, we describe a new reporter molecule whose bioluminescence activity within live cells and in mice can be used to measure Akt activity. Akt activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to activation or inhibition of receptor tyrosine kinase, inhibition of phosphoinositide 3-kinase, or direct inhibition of Akt. The results provide unique insights into the pharmacokinetics and pharmacodynamics of agents that modulate Akt activity, revealing the usefulness of this reporter for rapid dose and schedule optimization in the drug development process.
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Limin
authors: L
authors: Zhang
authors: Kuei C
authors: KC
authors: Lee
authors: Mahaveer S
authors: MS
authors: Bhojani
authors: Amjad P
authors: AP
authors: Khan
authors: Alla
authors: A
authors: Shilman
authors: Eric C
authors: EC
authors: Holland
authors: Brian D
authors: BD
authors: Ross
authors: Alnawaz
authors: A
authors: Rehemtulla
mesh_terms: D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D017931:DNA Primers; D005784:Gene Amplification; D017930:Genes, Reporter; D005910:Glioma; D006258:Head and Neck Neoplasms; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D010957:Plasmids; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt