Using expression vectors of TM-NLS compared to mutants further demonstrate the importance of the NLS for nucleolin interaction

A plethora of studies indicates that serotonin receptor 2A and 2C are involved in the regulation of appetite and energy homeostasis, although with functional differences between the genes. This region is known to regulate ErbB1 activity, since it mediates the nuclear localization of EGFR as well as receptor kinase activation. Tumors, like normal tissues, are composed of a heterogenous population of cells with variable capacity for self-renewal. Multipotent tumor cells with the capacity to self-renew and recapitulate the tumors from which they were derived following transplantation into immunocompromised mice are referred to as tumor initiating cells or cancer stem cells. However, other studies demonstrated that mutation of EGFR tripartite NLS or deletion of the ErbB2 tripartite NLS did not affect receptor protein membrane localization and activation of MAPK signaling. Although drug Rapamycin intake was reportedly higher in the middle-aged group we consider the influence of an occasional intake of antihistamins, atorvastatin, esomeprazol and the local application of pilocarpin negligible. The intake of L-Thyroxin by four middleaged individuals was deemed appropriate for normalisation of metabolic state. However, interferences of medication with autonomic function cannot be fully ruled out. In summary, our findings convincingly demonstrate that the algorithm of trigonometric regressive spectral analysis is able to map age- and gender-related variations in baroreflex function and autonomic tone. More importantly, using TRS we were able to describe adaption processes of the baroreceptor circuit during cardiovascular stimulation. Therefore, TRS may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when resting values appear to be normal. Irrespective of the methodical advantages TRS may be ideally suited for use in clinical care because the evaluation of very short data segments from spontaneous fluctuations in heart rate and blood pressure render time-consuming, strenuous or invasive procedures for BRS determination unnecessary. In our study we demonstrated that upon nucleolin or ligand stimulation the DNLS mutant of ErbB1 does not undergo phosphorylation. However, further examination of the receptor dimerization using BS3 crosslinker, demonstrated that EGF can induce DNLS mutant dimerization. Studies have shown that upon ligand binding the dimerization process starts from the extracellular region of EGFR. Hence, by using the cross linker we observed receptor dimerization, although the dimerization/activation process was not completed, as demonstrated by the lack of phosphorylation. Thus, EGF but not nucleolin can induce the dimerization of DNLS mutant. These results support our findings that the DNLS ErbB1 mutant does not interact with nucleolin.

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