EGF receptor activation: push comes to shove

A study by Zhang et al. (2006) in this issue of Cell provides compelling evidence that the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) is activated by the formation of an asymmetric dimer, with one kinase domain in the EGF-mediated dimer activating the other through an allosteric mechanism.     

Mapping out starvation responses

What are the pathways that underlie the coordinated responses of an organism to well-fed and food-deprived states? A report in this issue of Cell Metabolism suggests that starvation functions via a muscarinic acetylcholine receptor to activate MAP kinase signaling in the pharyngeal muscle of C. elegans (You et al., 2006).     

Using isoform-specific inhibitors to target lipid kinases

In this issue of Cell, Knight et al. (2006) present a detailed pharmacological analysis of the PI3 kinase (PI3-K) family using small molecule inhibitors. They conclude that p110alpha, a PI3-K isoform, has a critical role in insulin signaling. In a related Cancer Cell paper, Fan et al. (2006) show that blocking activation of both p110alpha and the kinase mTOR with a small molecule inhibitor limits the growth of gliomas.     

Making tubes: step by step

Branched hollow tubes form the architectural basis of many mammalian organs. The growth factor HGF/SF and its receptor, the Met receptor tyrosine kinase, stimulate epithelial cells to undergo tubulogenesis in vitro. In this issue of Developmental Cell, O'Brien et al. (2004) look at temporal regulation and the role of two HGF/SF effectors, the ERK 1/2 MAP kinases and matrix metalloproteases, in this process.     

The complex cartography of stem cell commitment

In this issue of Cell, a study by Adolfsson and coworkers (Adolfsson et al., 2005) provides insight into the early lineage commitment events of multipotent hematopoietic stem cells (HSCs). These studies demonstrate the importance of the Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate commitment in that erythrocyte and megakaryocyte potentials are lost first as HSCs differentiate to lymphocyte progenitors.     

Distinct and Dynamic Requirements for mTOR Signaling in Hematopoiesis and Leukemogenesis

Signaling involving PI3K and AKT regulates cell growth, partly through the mTOR kinase complexes 1 and 2. In this issue of Cell Stem Cell, Kalaitzidis et?al. and Magee et?al. reveal unique requirements for mTORC1 and mTORC2 signaling during blood development and leukemogenesis induced by loss of PTEN.     

Mdm2: p53's Lifesaver?

In a recent issue of Molecular Cell, Taira et al. (2007) and Rinaldo et al. (2007) provide insight into the involvement of the DYRK2 kinase and a surprising role of MDM2 in regulation of DNA damage-induced apoptosis via p53 phosphorylation.     

Wnt signaling went derailed again: a new track via the LIN-18 receptor?

In this issue of Cell, Inoue et al. (2004) reports that LIN-18, an atypical receptor tyrosine kinase related to mammalian Ryk and Drosophila Derailed, mediates Wnt signaling in parallel to LIN-17/Frizzled (Fz) during worm vulval development. LIN-18/Ryk and LIN-17/Fz appear to exhibit distinct Wnt specificity, and surprisingly, the LIN-18 intracellular domain may be dispensable.     

The Ripoptosome: death decision in the cytosol

In this issue of Molecular Cell, Tenev et al. and Feoktistova et al. describe the Ripoptosome, a cytosolic death-inducing RIP1-, FADD-, and caspase-8-containing complex that spontaneously assembles upon cIAP depletion, challenging the view that such complexes exclusively originate from receptor activation.     

A20: more than one way to skin a cat

In this issue of Molecular Cell, Skaug et al. (2011) propose a polyubiquitin-dependent, noncatalytic mechanism by which the deubiquitinase A20 inhibits IκB kinase and NF-κB activation.     

If the prophet does not come to the mountain: dynamics of signaling complexes in NF-kappaB activation

Recruitment of the NF-kappaB-activating IKK signaling complex to the TNF receptor is shown to be driven by induced binding of NEMO, a regulatory component of this complex, to K63-linked polyubiquitin chains attached to RIP1, a receptor-associated adaptor protein (Ea et al., 2006 [in a recent issue of Molecular Cell]; Li et al., 2006; Wu et al., 2006a).     

A polo match for Plk1

New work by Elia et al. in this issue of Cell reveals the molecular basis of phosphopeptide recognition by the polo domain and the domain's dual function to promote substrate recognition by targeting the kinase to subcellular structures and to autoregulate the adjacent protein kinase catalytic domain.     

CaMKII: new tricks for an old dog

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a pivotal signaling molecule in both the brain and the heart. In this issue of Cell, Erickson et al. (2008) demonstrate a mechanism for CaMKII activation by reactive oxygen species that provides a direct link between kinase activation and cardiac dysfunction.     

Regulation of Akt/PKB Ser473 phosphorylation

For years the Akt/PKB research field has been in turmoil, trying to understand how the activating phosphorylation of Akt/PKB at Ser473 is regulated. In the past month, papers in a recent issue of Molecular Cell (Gao et al., 2005) and in Science (Sarbassov et al., 2005) may have identified the phosphatase and kinase acting on this residue.     

Germline stem cells: the first guards of heredity

The genes involved in the cellular response to DNA damage are crucial for ensuring DNA integrity during spermatogenesis. In this issue of Cell Stem Cell, Takubo et al. (2008) show that ATM, a key kinase of the DNA damage response, is also involved in maintaining the stem cell potential of undifferentiated spermatogonia.     

A very private TGF-beta receptor embrace

In this issue of Molecular Cell, Groppe et al. (2008) describe the crystal structure of a six-element TGF-beta:receptor complex, addressing long-standing questions about the restrictive nature of this vital receptor interaction.     

Oncogenic mutations in B-Raf: some losses yield gains

A study by Wan et al. in this issue of Cell demonstrates that the majority of oncogenic mutations in the B-Raf protein kinase result in increased catalytic activity, through disruption of the autoinhibited state of the kinase domain. Surprisingly, several mutations lead to impaired B-Raf kinase activity, yet these mutants are nevertheless capable of stimulating downstream signaling through transactivation of C-Raf.     

Fixin' to divide

In this issue of Molecular Cell, Yata et?al. (2012) show that the mitotic kinase and cell-cycle regulator Plk1 can directly stimulate the DNA repair process, providing a potential mechanism of crosstalk between DNA repair and cell-cycle signaling.     

ATM breaks into heterochromatin

Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility.