The Peripheral Binding of 14-3-3γ to Membranes Involves Isoform-Specific Histidine Residues

Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states.This work was supported by grants from the Norwegian Cancer Society (to ØH), Junta de Andalucía, grant CVI-02483 (to JMSR), The Research Council of Norway (grant 185181 to A.M.), the Western Norway Health Authorities (grant 911618 to A.M.) and The Kristian Gerhard Jebsen Foundation (to AM)

Negative feedback regulation of the ERK1/2 MAPK pathway

The extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signalling pathway regulates many cellular functions, including proliferation, differentiation, and transformation. To reliably convert external stimuli into specific cellular responses and to adapt to environmental circumstances, the pathway must be integrated into the overall signalling activity of the cell. Multiple mechanisms have evolved to perform this role. In this review, we will focus on negative feedback mechanisms and examine how they shape ERK1/2 MAPK signalling. We will first discuss the extensive number of negative feedback loops targeting the different components of the ERK1/2 MAPK cascade, specifically the direct posttranslational modification of pathway components by downstream protein kinases and the induction of de novo gene synthesis of specific pathway inhibitors. We will then evaluate how negative feedback modulates the spatiotemporal signalling dynamics of the ERK1/2 pathway regarding signalling amplitude and duration as well as subcellular localisation. Aberrant ERK1/2 activation results in deregulated proliferation and malignant transformation in model systems and is commonly observed in human tumours. Inhibition of the ERK1/2 pathway thus represents an attractive target for the treatment of malignant tumours with increased ERK1/2 activity. We will, therefore, discuss the effect of ERK1/2 MAPK feedback regulation on cancer treatment and how it contributes to reduced clinical efficacy of therapeutic agents and the development of drug resistance

Contingencies between organizational identification and professional employee performance

Thesis (Ph. D.)--University of Washington, 2007.Organizational identification research demonstrates only weak support for the central hypothesis that organizational identification motivates employees to pursue organizational goals. I show that the influence of organizational identification on organization-benefiting behaviors is more complex than previously thought and depends on employees' (1) competing types of identification, such as professional identification, (2) perceptions regarding administrative treatment, and (3) perceptions regarding the prescribed organizational goal-attainment strategy. My first two studies show that the combination of organizational identification and professional identification influences the degree to which professionals engage in organization-benefiting behaviors. Moreover, I find that the combination of professional and organizational identification also influences the way that professionals behaviorally respond to perceived administrative treatment. In my first study I find that for professional employees who identify strongly with the organization and weakly with the profession, perceived beneficial and detrimental discretionary administrative treatment motivate better performance. In my second study I find that such professional employees are most likely to conform to administrative social influence and adopt technology that enhances organizational profitability and reduces professional service quality. Finally, in my third study, I demonstrate that the influence of organizational identification on professional employee performance depends on each employee's perception of the best organizational goal-attainment strategy. I find that highly organizationally identified professional employees who perceive the organization as prescribing a success-maximizing goal-attainment strategy have the lowest performance quality; whereas highly organizationally identified professional employees perceive the organization as prescribing a failure-minimizing strategy have the highest performance quality

An examination of whether and how leader humility enhances leader personal career success

Humble leaders are traditionally thought to create a great deal of human and social capital, yet be overshadowed by self‐promoting rivals for promotions. We propose that through informal career mentoring, humble leaders can improve their organizational status and promotability. We tested our model among a multisource sample of 610 leaders across 18 industries and 21 job functions who participated in a leader development program. Leader humility was reported by the focal leaders' peers, leader mentoring behavior was reported by the focal leaders' direct reports, leader status was reported by the focal leaders' immediate bosses, and leader promotability was reported by the focal leaders' superiors. Results generally confirmed that leader humility predicted leader mentoring behavior, which in turn predicted leader status, and ultimately higher leader promotability ratings. We discuss how our findings extend and enrich the literatures on leader humility and mentoring, showing how humble leaders can ascend organizational hierarchies.</p

Public negative labeling effects on team interaction and performance

Across four studies, we examine how public negative labeling, which is when a group member is publicly identified as bad, affects team performance. Across three experiments and one field study, we test and find support for our model, that public negative labeling undermines team performance via reduced perceptions of team interaction quality. Our study contributes to the expansive conversation on team effectiveness which highlights that “fighting fire with fire” in terms of public negative labeling is ineffective for dealing with uncivil workplace behavior

International finance : cases and simulation

vii, 392 p. ; 24 cm

Turnover Contagion: How Coworkers\u27 Job Embeddedness and Job Search Behaviors Influence Quitting

This research developed and tested a model of turnover contagion in which the job embeddedness and job search behaviors of coworkers influence employees’ decisions to quit. In a sample of 45 branches of a regional bank and 1,038 departments of a national hospitality firm, multilevel analysis revealed that coworkers’ job embeddedness and job search behaviors explain variance in individual “voluntary turnover” over and above that explained by other individual and group-level predictors. Broadly speaking, these results suggest that coworkers’ job embeddedness and job search behaviors play critical roles in explaining why people quit their jobs. Implications are discussed

Public negative labeling effects on team interaction and performance

Across four studies, we examine how public negative labeling, which is when a group member is publicly identified as bad, affects team performance. Across three experiments and one field study, we test and find support for our model, that public negative labeling undermines team performance via reduced perceptions of team interaction quality. Our study contributes to the expansive conversation on team effectiveness which highlights that “fighting fire with fire” in terms of public negative labeling is ineffective for dealing with uncivil workplace behavior

Deterring Juvenile Crime

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69004/2/10.1177_0044118X82013003006.pd