Negative Regulation of Receptor Tyrosine Kinases by T-cell Protein Tyrosine Phosphatase

Protein tyrosine phosphorylation controls a wide array of cellular responses such as growth, migration, proliferation, differentiation, metabolism and cytoskeletal organisation. Tyrosine phosphorylation is a dynamic process involving the competing activities of protein tyrosine kinases and protein tyrosine phosphatases. The protein tyrosine kinases are further divided into non-receptor- and receptor tyrosine kinases. The latter are transmembrane glycoproteins activated by the binding of specific ligands, mostly growth factors, to their extracellular domain, transmitting different signals to the cell. Growth factor receptors such as the epidermal growth factor receptor, vascular endothelial growth factor receptor 2 and platelet-derived growth factor receptor β, belong to the receptor tyrosine kinases, the signalling of which is often disturbed in various diseases, including cancer. This has led to the development of receptor tyrosine kinase antagonists for use as anti-cancer drugs. As the receptor tyrosine kinases, also the protein tyrosine phosphatases can be divided into receptor- and non-receptor types. The protein tyrosine phosphatases have attained much less attention than the receptor tyrosine kinases partly because they were identified later. However, accumulating evidence shows that the protein tyrosine phosphatases have important roles as specific and active regulators of tyrosine phosphorylation in cells and of physiological processes. Consequently, the protein tyrosine phosphatases are receiving arising interest as novel drug targets. The aim of this work was to elucidate the negative regulation of receptor tyrosine kinases by one non-receptor protein tyrosine phosphatase, T-cell protein tyrosine phosphatase TCPTP. The results show that TCPTP activated by cell adhesion receptor integrin α1 functions as a negative regulator of the epidermal growth factor receptor. It was also found that TCPTP affects vascular endothelial growth factor receptor 2 signalling and angiogenesis. Lastly, a High-throughput screen with 64,280 compounds was performed to identify novel TCPTP activators, resulting in identification of one small molecule compound capable of exerting similar effects on TCPTP signalling as integrin α1. This compound is shown to downregulate signalling of epidermal growth factor receptor and platelet-derived growth factor receptor β, as well as to inhibit cell proliferation and angiogenesis. Our results suggest that a suitable small-molecule TCPTP activator could be utilized in the development of novel anti-cancer drugs.

The effects of social networks on work-team effectiveness

This is a study of team social networks, their antecedents and outcomes. In focusing attention on the structural configuration of the team this research contributes to a new wave of thinking concerning group social capital. The research site was a random sample of Finnish work organisations. The data consisted of 499 employees in 76 teams representing 48 different organisations. A systematic literature review and quantitative methods were used in conducting the research: the former primarily to establish the current theoretical position on the relationships among the variables and the latter to test these relationships. Social network analysis was the primary method used in identifying the social-network relations among the work-team members. The first and key contribution of this study is that it relates the structuralnetwork properties of work teams to behavioural outcomes, attitudinal outcomes and, ultimately, team performance. Moreover, it shows that addressing attitudinal outcomes is also important in terms of team performance; attitudinal outcomes (team identity) mediated the relationship between the team’s performance and its social network. The second contribution is that it examines the possible antecedents of the social structure. It is thus one response to Salancik’s (1995) call for a network theory in that it explains why certain network characteristics exist. Itdemonstrates that irrespective of whether or not a team is heterogeneous in terms of age or gender, educational diversity may protect it from centralisation. However, heterogeneity in terms of gender turned out to have a negative impact on density. Thirdly, given the observation that the benefits of (team) networks are typically theorised and modelled without reference to the nature of the relationships comprising the structure, the study directly tested whether team knowledge mediated the effects of instrumental and expressive network relationships on team performance. Furthermore, with its focus on expressive networks that link the workplace to a more informal world, which have been rather neglected in previous research, it enhances knowledge of teams andnetworks. The results indicate that knowledge sharing fully mediates the influence of complementarities between dense and fragmented instrumental network relationships, thus providing empirical validation of the implicit understanding that networks transfer knowledge. Fourthly, the study findings suggest that an optimal configuration of the work-team social-network structure combines both bridging and bonding social relationships.

Life-related negative customer emotions in real estate agent encounters

The goal of this study was to explore how do customers’ life-related negative emotions affect real estate business. This was divided into two research questions: 1. What life-related negative emotions can be recognised in real estate customer encounters? 2. How do the recognised emotions affect customer encounters and the realtor’s work? 3. How can the realtor take the emotions into account in customer service? The theoretical background consists of two main lines of study: emotions and customer encounters. A wide literary review on emotions research was conducted from a cognitive psychology point of view, focusing on negative emotions. Emotions research was then combined into the field of customer encounters. Qualitative study was chosen as the methodological basis of the study. Empirical material of this study was collected through in-depth interviews with 13 successful Finnish real estate agents. Narrative research was used as a method for the study. Four life-related emotion categories were recognized in real estate customer encounters: sadness, anger, anxiety and shame. These emotions rose from issues varying from death of a close one to divorce and from major changes in life stages to deep emotional attachment to an old home. The study also found that these incidental negative emotions do affect customer encounters and realtors’ work. The emotions affected the decision making of customers and sometimes overshadowed reason. Some emotions made the customer passive and slow to make any decisions, while others made their decision making fast and hasty. Even though the incidental emotions might not have had anything to do with the real estate deal, they could affect the outcome of the customer encounter and the whole real estate deal. Interestingly enough, the study found that not all successful real estate agents knowingly serve customers in an emotional level. The study does, however, suggest that in fact it may be an ethical decision of the customer server to take into account the emotional state of the customer. Attending to the emotional side of customers does not only increase pleasantness of the customer encounter, but may improve and balance customer decision making and prevent hasty decisions possibly leading to improved customer satisfaction. This study also gave practical managerial implications to customer service providers on how negative incidental emotions can be attended to in a customer encounter. This study could be useful not only to real estate agents, but also in other types of customer service, especially with vulnerable populations or other types of home-related business.