A Trauma-Informed Mentoring Framework for Forensic Nurses: An Overview of STEERR-Structure, Process, and Evaluation.

The STEERR Mentoring Framework, grounded in decolonized and feminist mentorship approaches, integrates foundational principles of mentoring with the unique and complex characteristics of the role of the forensic nurse. The primary objective of the program is to support a competent, sustainable, and resilient forensic nursing workforce. In this article, we describe the development process, framework structure, and evaluation approach implemented within a 1-year pilot initiative focused on forensic nurses in the sexual assault nurse examiner role.

Phosphorylation of the C-Raf N Region Promotes Raf Dimerization.

The activation of Raf kinases by the small GTPase Ras requires two major sets of phosphorylations. One set lies within the activation loop, and the other lies within the N-terminal acidic region (N region). In the most abundant isoform of Raf, C-Raf, N-region phosphorylations occur on serine 338 (S338) and tyrosine 341 (Y341) and are thought to provide allosteric activation of the Raf dimer.

Phosphorylation of Rap1 by cAMP-dependent Protein Kinase (PKA) Creates a Binding Site for KSR to Sustain ERK Activation by cAMP.

Cyclic adenosine monophosphate (cAMP) is an important mediator of hormonal stimulation of cell growth and differentiation through its activation of the extracellular signal-regulated kinase (ERK) cascade. Two small G proteins, Ras and Rap1 have been proposed to mediate this activation. Using HEK293 cells as a model system, we have recently shown that both Ras and Rap1 are required for cAMP signaling to ERKs.

Protein Kinase A-independent Ras Protein Activation Cooperates with Rap1 Protein to Mediate Activation of the Extracellular Signal-regulated Kinases (ERK) by cAMP.

Cyclic adenosine monophosphate (cAMP) is an important mediator of hormonal stimulation of cell growth and differentiation through its activation of the extracellular signal-regulated kinase (ERK) cascade. Two small G proteins, Ras and Rap1, have been proposed to mediate this activation, with either Ras or Rap1 acting in distinct cell types. Using Hek293 cells, we show that both Ras and Rap1 are required for cAMP signaling to ERKs.

Protein kinase A-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration.

The small G protein Rap1 can mediate "inside-out signaling" by recruiting effectors to the plasma membrane that signal to pathways involved in cell adhesion and cell migration. This action relies on the membrane association of Rap1, which is dictated by post-translational prenylation as well as by a stretch of basic residues within its carboxyl terminus. One feature of this stretch of acidic residues is that it lies adjacent to a functional phosphorylation site for the cAMP-dependent protein kinase PKA.

B-Raf is required for positive selection and survival of DP cells, but not for negative selection of SP cells.

The duration of signaling through the MAP kinase (or ERK pathway) cascade has been implicated in thymic development, particularly positive and negative selection. In T cells, two isoforms of the MAP kinase kinase kinase Raf function to transmit signals from the T-cell receptor to ERK: C-Raf and B-Raf. In this study, we conditionally ablated B-Raf expression within thymocytes to assess the effects on ERK activation and thymocyte development.

The interaction of Epac1 and Ran promotes Rap1 activation at the nuclear envelope.

Epac1 (exchange protein directly activated by cyclic AMP [cAMP]) couples intracellular cAMP to the activation of Rap1, a Ras family GTPase that regulates cell adhesion, proliferation, and differentiation. Using mass spectrometry, we identified the small G protein Ran and Ran binding protein 2 (RanBP2) as potential binding partners of Epac1. Ran is a small G protein best known for its role in nuclear transport and can be found at the nuclear pore through its interaction with RanBP2.

Ras is required for the cyclic AMP-dependent activation of Rap1 via Epac2.

Exchange proteins activated by cAMP (cyclic AMP) 2 (Epac2) is a guanine nucleotide exchange factor for Rap1, a small G protein involved in many cellular functions, including cell adhesion, differentiation, and exocytosis. Epac2 interacts with Ras-GTP via a Ras association (RA) domain. Previous studies have suggested that the RA domain was dispensable for Epac2 function.

Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation.

Like other small G proteins of the Ras superfamily, Rap1 is activated by distinct guanine nucleotide exchange factors (GEFs) in response to different signals to elicit cellular responses. Activation of Rap1 by cyclic AMP (cAMP) can occur via cAMP-dependent protein kinase A (PKA)-independent and PKA-dependent mechanisms. PKA-independent activation of Rap1 by cAMP is mediated by direct binding of cAMP to Rap1-guanine nucleotide exchange factors (Rap1-GEFs) Epac1 (exchange protein directly activated by cAMP 1) and Epac2 (Epac1 and Epac2 are also called cAMP-GEFI and -GEFII).

Multiple roles of Rap1 in hematopoietic cells: complementary versus antagonistic functions.

Small G proteins serve as critical control points in signal transduction, integrating a wide range of stimuli to dictate discrete cellular outcomes. The outcomes of small G-protein signaling can both potentiate and antagonize one another. Studies in hematopoietic cells have uncovered multiple functions for the small G protein, Rap1 (Ras-proximate-1).

Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by the costimulatory molecule CTLA-4.

The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) is activated following engagement of the T-cell receptor and is required for interleukin 2 (IL-2) production and T-cell proliferation. This activation is enhanced by stimulation of the coreceptor CD28 and inhibited by the coreceptor CTLA-4. We show that the small G protein Rap1 is regulated in the opposite manner; it is inhibited by CD28 and activated by CTLA-4.

PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells.

Recent studies suggest that the tyrosine kinase Src plays an important role in the hormonal regulation of extracellular signal-regulated kinases (ERKs) via cyclic AMP (cAMP). Src has also been proposed to mediate signals downstream of nerve growth factor (NGF). Here, we report that the cAMP-dependent protein kinase A (PKA) induced the phosphorylation of Src at residue serine17 (S17) in multiple cell types including PC12, Hek293, AtT-20 and CHO cells.

Ectopic B-Raf expression enhances extracellular signal-regulated kinase (ERK) signaling in T cells and prevents antigen-presenting cell-induced anergy.

T cells that receive stimulation through the T cell receptor (TCR) in the absence of costimulation become anergic and are refractory to subsequent costimulation. This unresponsiveness is associated with the constitutive activation of the small G protein, Rap1, and the lack of Ras-dependent activation of ERK. Recent studies suggest that Rap1 can activate the MAP kinase kinase kinase B-Raf that is either endogenously or ectopically expressed.