Neuronal function depends on the specification of neuronal processes as axons or dendrites. In this issue of Genes & Development Choi and colleagues (2485-2495) show that without Tuberous Sclerosis Complex 1 (Tsc1) or Tsc2, molecules linked to the autosomal dominant disease tuberous sclerosis, an increase in the activity of the translational regulator Target of Rapamycin 1 (TORC1) causes neuron...

Poxviruses include medically important human pathogens, yet little is known about the specific cellular factors essential for their replication. To identify genes essential for poxvirus infection, we used high-throughput RNA interference to screen the Drosophila kinome for factors required for vaccinia infection. We identified seven genes including the three subunits of AMPK as promoting vaccin...

Gradients of soluble attractants as well as extracellular matrix (ECM) proteins serve as cues for directional cell movement. Such "chemotaxis" and "haptotaxis" steers migration of cells during embryonic development, wound healing, and immune responses. In this issue, Chan et al. (2014. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201404067) show that the tumor suppressor LKB1 controls haptotaxis...

Adenosine monophosphate-activated protein kinase (AMPK), a metabolic protein kinase, and its upstream kinase LKB1 play crucial roles in the establishment and maintenance of cell polarity. Although the shapes of polarized cells display extraordinary diversity, the key molecules involved in cell polarity are relatively well conserved. Here, we review the mechanisms and factors responsible for org...

LKB1, the product of a tumour suppressor gene, is a serine/threonine kinase that coordinates disparate cellular processes. Recent data have revealed novel functions for LKB1, providing new insight into the regulation of cell polarity and energy-generating metabolism.

Mutations in the serine-threonine kinase (LKB1) lead to a gastrointestinal hamartomatous polyposis disorder with increased predisposition to cancer (Peutz-Jeghers syndrome). LKB1 has many targets, including the AMP-activated protein kinase (AMPK) that is phosphorylated under low-energy conditions. AMPK phosphorylation in turn, affects several processes, including inhibition of the target of rap...

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Although the clinical success rate for the treatment of early-stage HCC has improved, the prognosis of advanced HCC remains poor owing to the high recurrence rate and the refractory nature of HCC for various anticancer drugs. A better understanding of the pathogenesis of HCC is therefore critically needed i...

The tumor suppressor kinase LKB1 has been identified as a physiologic activator of the key metabolic regulator 5'-AMP-activated protein kinase, establishing a possible molecular link between the regulation of metabolism and cell proliferation.

How can a constitutively active 'master' kinase with numerous downstream targets preferentially phosphorylate one or more of these without influencing all simultaneously? How might such a system be switched off? The characterization of the role of deubiquitination in regulating the phosphorylation and activation of AMPK (AMP-activated protein kinase)-related kinases by LKB1 suggests a novel and...