Deciphering signaling pathways in vivo: the Ras/Raf/MEK/ERK cascade.

The Ras/Raf/MEK/ERK cascade is a highly conserved signal transduction module, whose activation results in a number of different physiological outcomes. Depending on the cell type or the stimulus used, the pathway has been implicated in proliferation, differentiation, apoptosis, and migration. Because of this wide range of activities, these kinases are considered attractive (anticancer) therapeutic targets.

Raf-1 addiction in Ras-induced skin carcinogenesis.

Ras activation is common to many human cancers and promotes cell proliferation and survival by initiating multiple signaling cascades. Accordingly, Ras-transformed cells are generally considered too resourceful to become addicted to a single effector. In contrast to this tenet, we now demonstrate an absolute, cell autonomous requirement for Raf-1 in the development and maintenance of Ras-induced skin epidermis tumors.

A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal.

Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. Here we describe a previously uncharacterized, unexpected role of Mek1 in downregulating Mek2-dependent Erk signaling. Mek1 mediates the regulation of Mek2 in the context of a previously undiscovered Mek1-Mek2 complex.

Essential role of B-Raf in oligodendrocyte maturation and myelination during postnatal central nervous system development.

Mutations in the extracellular signal-regulated kinase (ERK) pathway, particularly in the mitogen-activated protein kinase/ERK kinase (MEK) activator B-Raf, are associated with human tumorigenesis and genetic disorders. Hence, B-Raf is a prime target for molecule-based therapies, and understanding its essential biological functions is crucial for their success. B-Raf is expressed preferentially in cells of neuronal origin.

ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts.

The Raf/MEK/ERK cascade is a highly conserved signal transduction module whose activation reportedly results in a plethora of physiological outcomes. Depending on the cell type or the stimulus used, the pathway has been implicated in proliferation, differentiation, survival, and migration. Their wide range of activities renders the component of the Raf/MEK/ERK pathway prime candidates for molecule-targeted therapies, in particular, but not exclusively, in the context of cancer.

Essential role of B-Raf in ERK activation during extraembryonic development.

The kinases of the Raf family have been intensively studied as activators of the mitogen-activated protein kinase kinase/extra-cellular signal-regulated kinase (ERK) module in regulated and deregulated proliferation. Genetic evidence that Raf is required for ERK activation in vivo has been obtained in lower organisms, which express only one Raf kinase, but was hitherto lacking in mammals, which express more than one Raf kinase. Ablation of the two best studied Raf kinases, B-Raf and Raf-1, is lethal at midgestation in mice, hampering the detailed study of the essential functions of these proteins.

Steroid receptors in canine endometrial cells can be regulated by estrogen and progesterone under in vitro conditions.

The expression of estrogen (ER) and progesterone receptors (PR) in the endometrium is regulated by steroid hormones. An increase in plasma estrogen leads to upregulation of the number of both steroid receptors, whereas a decrease in both receptors population is due to high concentration of plasma progesterone. To study the exact effect of different concentrations of beta-estradiol and progesterone on canine epithelial and stromal endometrial cells an in vitro model from dog uterus was developed and kept for 20 days.