To understand the mechanisms by which electrical activity may generate long-term responses in the nervous system, we examined how activation of voltage-sensitive calcium channels (VSCCs) can stimulate the Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Calcium influx through L-type VSCCs leads to tyrosine phosphorylation of the adaptor protein Shc and its association with the ada...

The human airway is lined with respiratory epithelial cells, which create a critical barrier through the formation of apical tight junctions. To investigate the molecular mechanisms underlying this process, an RNAi screen for guanine nucleotide exchange factors (GEFs) was performed in human bronchial epithelial cells (16HBE). We report that SOS1, acting through the Ras/MEK/ERK pathway, is essen...

The precise mechanisms via which Rac1 is activated by cadherin junctions are not fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR signalling, but how EGFR does so is unclear. To address which activator could mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs, SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and le...

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like confo...

Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and Ras guanine nucleotide releasing protein (RasGRP), have been implicated in controlling Ras activation when cell surface receptors are stimulated. To address the specificity or redundancy of these exchange factors, we have generated Sos1/Sos2 double- or RasGRP3-deficient B cell lines and determined their ability to...

To date, no gene expression comparisons have been conducted between highly salt tolerant halophytes and related glycophytes. Therefore, I investigated the effects of salinity on ion accumulation and expression of candidate salt tolerance genes in the highly tolerant salt accumulating halophyte Salicornia dolichostachya and the taxonomically related glycophytic Spinacia oleracea. S. dolichostach...

سیستم حمل‌ونقل ریلی از تعامل مجموعه‌ای تجهیزات و عملیات تشکیل‌ شده است که توانایی ظرفیت یک در بار مسافر را تعیین می‌کند. بدین‌منظور، محاسبة پیش‌بینی نحوة تغییرات آن مهم شناخت آن‌ کمک شایانی به ارتقای سطح بهره‌برداری شبکة روش‌های گوناگونی برای وجود دارد با توجه نوع شبکه شیوة استفاده این روش‌ها، می‌توان آنها بهره گرفت. ظرفیت، توانمندی‌های سیستم‌های اطلاعات مکانی می‌شود تحت وب، وضعیت ظرفیتی عملیات...