Using kinomics to delineate signaling pathways: control of CRTC2/TORC2 by the AMPK family.
The classical role of AMP-activated protein kinase (AMPK) as an energy status sensor is expanding to include other members of the AMPK family. Recent genetic and cell biological evidence points to a role for MAP/microtubule affinity-regulating kinase 2 (MARK2/EMK/Par1b) in the regulation of metabolic events as well as in the control of CREB-dependent transcription activated by glucose in pancreatic islet beta cells. We have recently developed an in vitro kinase screening platform to identify novel kinase:substrate pairs, the building blocks of signal transduction pathways. Application of this technology led us to identify MARK2 as the kinase that targets a novel glucose-regulated phosphorylation site on Transducer of Regulated CREB Activity 2 (TORC2, referred to as CREB-Regulated Transcriptional Coactivator 2, or CRTC2), a transcriptional coactivator essential for CREB activity in beta cells. We discuss these recent developments and suggest a model whereby members of the AMPK family integrate numerous signals to coordinate energy metabolism and cellular polarity with gene expression to regulate cell function/proliferation.
Fu
Accalia
A
Apoptosis Research Centre, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Screaton
Robert A
RA
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C493245:CRTC2 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors; C094670:MARK2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases