The actin cytoskeleton mediates a variety of essential biological functions in all eukaryotic cells. In addition to providing a structural framework around which cell shape and polarity are defined, its dynamic properties provide the driving force for cells to move and to divide. Understanding the biochemical mechanisms that control the organization of actin is thus a major goal of contemporary cell biology, with implications for health and disease. Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and furthermore, through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.

/pdf/rho-gtpases-and-the-actin-cytoskeleton-zsfyn1yhxi.pdf

Rho GTPases and the Actin Cytoskeleton

AKT/PKB signaling: navigating downstream.

The evolutionarily conserved checkpoint protein kinase, TOR (target of rapamycin), has emerged as a major effector of cell growth and proliferation via the regulation of protein synthesis. Work in the last decade clearly demonstrates that TOR controls protein synthesis through a stunning number of downstream targets. Some of the targets are phosphorylated directly by TOR, but many are phosphorylated indirectly. In this review, we summarize some recent developments in this fast-evolving field. We describe both the upstream components of the signaling pathway(s) that activates mammalian TOR (mTOR) and the downstream targets that affect protein synthesis. We also summarize the roles of mTOR in the control of cell growth and proliferation, as well as its relevance to cancer and synaptic plasticity.

/pdf/upstream-and-downstream-of-mtor-2v5cvgfhmb.pdf

Upstream and downstream of mTOR

https://www.cell.com/cell/pdf/S0092-8674(03)00929-2.pdf

TSC2 mediates cellular energy response to control cell growth and survival.

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.

/pdf/mtor-from-growth-signal-integration-to-cancer-diabetes-and-503skey4mb.pdf

mTOR: from growth signal integration to cancer, diabetes and ageing

Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton

http://genetics.wustl.edu/bio5491/files/2012/02/Tapon_Salvador_Cell.pdf

salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines

Intense research over the past four years has led to the discovery and characterization of a novel signalling network, known as the Salvador-Warts-Hippo (SWH) pathway, involved in tissue growth control in Drosophila melanogaster. At present, eleven proteins have been implicated as members of this pathway, and several downstream effector genes have been characterized. The importance of this pathway is emphasized by its evolutionary conservation, and by increasing evidence that its deregulation occurs in human tumours. Here, we review the main findings from Drosophila and the implications that these have for tumorigenesis in mammals.

Nicolas Tapon

Papers

Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton

salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines

The Salvador–Warts–Hippo pathway — an emerging tumour-suppressor network

Rac and Cdc42 Induce Actin Polymerization and G1 Cell Cycle Progression Independently of p65PAK and the JNK/SAPK MAP Kinase Cascade

The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.