Biomedical subjects

Ali Zarrinpar

Publications and source records attributed to Ali Zarrinpar.

5 recordsLinked to original sources

PubMed2006

Sharp recanalization of a short esophageal occluding stricture in a patient with epidermolysis bullosa.

BACKGROUND: Although esophageal strictures caused by epidermolysis bullosa are often treated with balloon dilations, complete obstruction has few effective therapies except esophagectomy with colonic replacement. OBJECTIVE: Resolution of esophageal obstructive lesion without surgical intervention. DESIGN: Case study. SETTING: Interventional radiology. PATIENT: Epidermolysis bullosa with esophageal stricture. INTERVENTION: Endoscopic- and guidewire-guided sharp recanalization. MAIN OUTCOME MEASUREMENT: Radiologic evidence of stricture resolution. RESULTS: Successful recanalization. LIMITATIONS: Experience of operators (anesthesiologist, endoscopist, interventional radiologist). CONCLUSIONS: Sharp recanalization of a complete stricture in patients with epidermolysis bullosa is feasible in a controlled setting.

Adult↗

PubMed2004

Sho1 and Pbs2 act as coscaffolds linking components in the yeast high osmolarity MAP kinase pathway.

Scaffold proteins mediate efficient and specific signaling in several mitogen-activated protein (MAP) kinase cascades. In the yeast high osmolarity response pathway, the MAP kinase kinase Pbs2 is thought to function as a scaffold, since it binds the osmosensor Sho1, the upstream MAP kinase kinase kinase Ste11, and the downstream MAP kinase Hog1. Nonetheless, previous work has shown that Ste11 can be activated even when Pbs2 is deleted, resulting in inappropriate crosstalk to the mating pathway. We have found a region in the C terminus of Sho1 that binds Ste11 independently of Pbs2 and is required for crosstalk. These data support a model in which Sho1 has at least two separable interaction regions: one that binds Ste11 and mediates its activation, and one that binds Pbs2, directing Ste11 to act on Pbs2. Thus, a network of interactions provided by both Sho1 and Pbs2 appears to direct pathway information flow.

MAP Kinase Kinase Kinases↗

PubMed2003

Optimization of specificity in a cellular protein interaction network by negative selection.

Most proteins that participate in cellular signalling networks contain modular protein-interaction domains. Multiple versions of such domains are present within a given organism: the yeast proteome, for example, contains 27 different Src homology 3 (SH3) domains. This raises the potential problem of cross-reaction. It is generally thought that isolated domain-ligand pairs lack sufficient information to encode biologically unique interactions, and that specificity is instead encoded by the context in which the interaction pairs are presented. Here we show that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity--no other SH3 domain present in the yeast genome cross-reacts with the Pbs2 peptide, in vivo or in vitro. Such high specificity, however, is not observed in a set of non-yeast SH3 domains, and Pbs2 motif variants that cross-react with other SH3 domains confer a fitness defect, indicating that the Pbs2 motif might have been optimized to minimize interaction with competing domains specifically found in yeast. System-wide negative selection is a subtle but powerful evolutionary mechanism to optimize specificity within an interaction network composed of overlapping recognition elements.

Amino Acid Motifs↗

PubMed2003

The structure and function of proline recognition domains.

One particularly abundant group of modular recognition domains consists of those that bind proline-rich motifs. Such modules, including the SH3, WW, and EVH1 domains, play a critical role in the assembly and regulation of many intracellular signaling complexes. These domains use strikingly similar molecular mechanisms of proline recognition. We discuss some of the potential biological advantages conferred by proline recognition, which may explain its widespread use in signaling.

Animals↗

PubMed2003

Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms.

How scaffold proteins control information flow in signaling pathways is poorly understood: Do they simply tether components, or do they precisely orient and activate them? We found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling. Moreover, by engineering a scaffold that tethers a unique kinase set, we could create a synthetic MAP kinase pathway with non-natural input-output properties. These findings demonstrate that scaffolds are highly flexible organizing factors that can facilitate pathway evolution and engineering.

Adaptor Proteins, Signal Transducing↗