The impact of extensive loss of telecommunications on general practice: A case study in rural Victoria.

Objective: To describe the impact of major loss of telecommunications on general practice in a rural region of Australia.

Design: A multi-stage qualitative study. Purposively selected participants were invited to contribute to initial data collection using an online survey, followed by interviews with selected participants.

B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms.

B-Raf is a key regulator of the ERK pathway and is mutationally activated in two-thirds of human melanomas. In this work, we have investigated the activation mechanism of B-Raf and characterized the roles of Ras and of B-Raf phosphorylation in this regulation. Raf-1 is regulated by an N-terminal autoinhibitory domain whose actions are blocked by interaction with Ras and subsequent phosphorylation of Ser(338).

Characterization of the biochemical and transforming properties of the neuroepithelial transforming protein 1.

Rho family small G proteins are key regulators of cytoskeletal organization and oncogenic transformation whose activation is controlled by a family of proteins known as guanine nucleotide exchange factors (GEFs). In this work we have characterized the structural and biological determinants for cytoskeletal regulation and cell transformation by the neuroepithelioma transforming gene 1 (NET1), which is a GEF specific for RhoA, but not Cdc42 or Rac1. Previously it was shown that the biological activity and nuclear localization of NET1 is controlled by its amino terminus.

Phosphorylation of Raf-1 by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition.

Exposure of cells to mitogens or growth factors stimulates Raf-1 activity through a complex mechanism that involves binding to active Ras, phosphorylation on multiple residues, and protein-protein interactions. Recently it was shown that the amino terminus of Raf-1 contains an autoregulatory domain that can inhibit its activity in Xenopus oocytes. In the present work we show that expression of the Raf-1 autoinhibitory domain blocks extracellular signal-regulated kinase 2 activation by the Raf-1 catalytic domain in mammalian cells.