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Biomedical subjects

Walid Sabbagh

Publications and source records attributed to Walid Sabbagh.

4 recordsLinked to original sources
PubMed2004

A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast.

Signaling molecules such as Cdc42 and mitogen-activated protein kinases (MAPKs) can function in multiple pathways in the same cell. Here, we propose one mechanism by which such factors may be directed to function in a particular pathway such that a specific response is elicited. Using genomic approaches, we identify a new component of the Cdc42- and MAPK-dependent signaling pathway that regulates filamentous growth (FG) in yeast. This factor, called Msb2, is a FG-pathway-specific factor that promotes differential activation of the MAPK for the FG pathway, Kss1. Msb2 is localized to polarized sites on the cell surface and interacts with Cdc42 and with the osmosensor for the high osmolarity glycerol response (HOG) pathway, Sho1. Msb2 is glycosylated and is a member of the mucin family, proteins that in mammalian cells promote disease resistance and contribute to metastasis in cancer cells. Remarkably, loss of the mucin domain of Msb2 causes hyperactivity of the FG pathway, demonstrating an inhibitory role for mucin domains in MAPK pathway activation. Taken together, our data suggest that Msb2 is a signaling mucin that interacts with general components, such as Cdc42 and Sho1, to promote their function in the FG pathway.

Amino Acid Sequence↗
PubMed2004

A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1.

The Saccharomyces cerevisiae mitogen-activated protein kinases (MAPKs) Fus3 and Kss1 bind to multiple regulators and substrates. We show that mutations in a conserved docking site in these MAPKs (the CD/7m region) disrupt binding to an important subset of their binding partners, including the Ste7 MAPK kinase, the Ste5 adaptor/scaffold protein, and the Dig1 and Dig2 transcriptional repressors. Supporting the possibility that Ste5 and Ste7 bind to the same region of the MAPKs, they partially competed for Fus3 binding. In vivo, some of the MAPK mutants displayed reduced Ste7-dependent phosphorylation, and all of them exhibited multiple defects in mating and pheromone response. The Kss1 mutants were also defective in Kss1-imposed repression of Ste12. We conclude that MAPKs contain a structurally and functionally conserved docking site that mediates an overall positively acting network of interactions with cognate docking sites on their regulators and substrates. Key features of this interaction network appear to have been conserved from yeast to humans.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Upper labial deficiency in Mobius syndrome: a previously unreported feature and its correction.

Bilateral facial palsy in Möbius syndrome remains one of the greatest challenges in reconstructive plastic surgery. Facial reanimation is an invaluable aid to such patients because it allows for greater social interaction by means of the ability to smile. In performing facial reanimation surgery on patients with Möbius syndrome, it is the observation of the senior author (Harrison) that upper labial deficiency is a consistent and previously unreported feature of the syndrome. It has been the practice of the senior author to perform upper labial augmentation on Möbius syndrome patients by insertion of a lipodermal autograft, in addition to facial reanimation. Nine patients with Möbius syndrome who presented to the Department of Plastic Surgery during an 8-year period were reviewed. All nine possessed bilateral facial palsy and upper labial deficiency in addition to other abnormalities consistent with Möbius syndrome. Six patients underwent bilateral facial reanimation and upper labial augmentation alone. One patient refused facial reanimation surgery but consented to upper labial augmentation. One patient, with concomitant micrognathia, underwent bilateral facial reanimation, upper labial augmentation, and insertion of a Silastic chin implant. In one patient, a child who also exhibited micrognathia, bilateral facial reanimation alone was carried out, with further procedures for upper labial and chin cosmesis being postponed until adulthood. The indication for performing upper labial augmentation was cosmetic. The procedure improved upper labial appearance and restored balance to the mouth. Patients also expressed higher satisfaction with eating and drinking, which they related to the improved fullness of the upper lip. This was before the facial reanimation had become functional. Upper labial deficiency warrants addition to the list of facial features of Möbius syndrome and is something that must be assessed in the context of facial reanimation surgery.

Adolescent↗