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Full-Text Articles in Medicine and Health Sciences
An Intramolecular Association Between Two Domains Of The Protein Kinase Fused Is Necessary For Hedgehog Signaling, Manuel Ascano Jr., David J. Robbins
An Intramolecular Association Between Two Domains Of The Protein Kinase Fused Is Necessary For Hedgehog Signaling, Manuel Ascano Jr., David J. Robbins
Dartmouth Scholarship
The protein kinase Fused (Fu) is an integral member of the Hedgehog (Hh) signaling pathway. Although genetic studies demonstrate that Fu is required for the regulation of the Hh pathway, the mechanistic role that it plays remains largely unknown. Given our difficulty in developing an in vitro kinase assay for Fu, we reasoned that the catalytic activity of Fu might be highly regulated. Several mechanisms are known to regulate protein kinases, including self-association in either an intra- or an intermolecular fashion. Here, we provide evidence that Hh regulates Fu through intramolecular association between its kinase domain (ΔFu) and its carboxyl-terminal …
A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade
A Vibrio Cholerae Classical Tcpa Amino Acid Sequence Induces Protective Antibody That Binds An Area Hypothesized To Be Important For Toxin-Coregulated Pilus Structure, Ronald K. Taylor, Thomas J. Kirn, Michael D. Meeks, Terri K. Wade, William F. Wade
Dartmouth Scholarship
Vibrio cholerae is a gram-negative bacterium that has been associated with cholera pandemics since the early 1800s. Whole-cell, killed, and live-attenuated oral cholera vaccines are in use. We and others have focused on the development of a subunit cholera vaccine that features standardized epitopes from various V. cholerae macromolecules that are known to induce protective antibody responses. TcpA protein is assembled into toxin-coregulated pilus (TCP), a type IVb pilus required for V. cholerae colonization, and thus is a strong candidate for a cholera subunit vaccine. Polypeptides (24 to 26 amino acids) in TcpA that can induce protective antibody responses have …
A Novel Triterpenoid Induces Transforming Growth Factor Β Production By Intraepithelial Lymphocytes To Prevent Ileitis, Laurie A. Minns, Dominique Buzoni-Gatel, Kenneth H. Ely, Nicolas Rachinel, Souphalone Luangsay, Lloyd H. Kasper
A Novel Triterpenoid Induces Transforming Growth Factor Β Production By Intraepithelial Lymphocytes To Prevent Ileitis, Laurie A. Minns, Dominique Buzoni-Gatel, Kenneth H. Ely, Nicolas Rachinel, Souphalone Luangsay, Lloyd H. Kasper
Dartmouth Scholarship
The loss of homeostasis is a hallmark of inflammatory bowel disease. Oral infection of susceptible mice with Toxoplasma gondii results in an acute lethal ileitis characterized by increased interferon γ, tumor necrosis factor α, and inducible nitric oxide synthase; homeostasis results from transforming growth factor β production by intraepithelial lymphocytes. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) is a potent anti-inflammatory molecule previously shown in vitro to suppress the de novo synthesis of inducible nitric oxide synthase and to induce the transcription and activation of genes from the transforming growth factor β signaling pathway. We evaluated the immune response in …
The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley
The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley
Dartmouth Scholarship
AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its …