Samuel N. Young

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

Jiyi Pang, Aysha Al‐Ani, Komal M. Patel, Yunzhuo Zhou et autres

Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Although current therapies aim to correct these imbalances to induce remission, most patients ultimately relapse, suggesting that key pathogenic mechanisms persist. Here, …

au, us, cn, kr, de, gb (code pays fourni par la source)

An Ancestral Mechanism of Calmodulin Binding to Cds1 Kinase Inhibits Catalytic Activity

Stephanie A. Manovella, Tingting Wang, Samuel N. Young, Toby A. Dite et autres

ABSTRACT Calmodulin is a highly conserved, calcium (Ca 2+ ) sensor protein that is ubiquitous among eukaryotes. Ca 2+ binding to Calmodulin induces a conformational change that facilitates interaction with, and activation of, serine/threonine protein kinases, including members of the CaMK family. …

au, us (code pays fourni par la source)

A novel gain of function variant in NUAK2 causes oculomotor apraxia in a three-generation family

Manjekah Dunn, Janine Smith, Christopher R. Horne, Meredith Wilson et autres

au (code pays fourni par la source)

Impact of BECLIN1 haploinsufficiency on goblet cell function and susceptibility to colitis

Juliani Juliani, Sharon Tran, Tiffany J. Harris, Sarah L. Ellis et autres

Abstract BECLIN1 is a central regulator of autophagy and endocytic trafficking essential for epithelial homoeostasis. While complete intestinal epithelial loss of BECLIN1 causes fatal enteritis originating in the small intestine, the consequences of its partial loss in the gut remain unclear. Given …

au (code pays fourni par la source)

The kinase domain of RIPK3 tunes its scaffolding functions

Shene Chiou, Christopher R. Horne, Komal M. Patel, Adele Preaudet et autres

Abstract The pro-inflammatory programmed cell death pathway, necroptosis, relies on phosphorylation of the terminal effector, MLKL, by RIPK3. RIPK3-deficient mice or those harboring the kinase-inactivating mutation, RIPK3 K51A , are ostensibly normal in the absence of challenge, indicating that RIPK3 and its …

au, us (code pays fourni par la source)

Unconventional binding of calmodulin to CHK2 kinase inhibits catalytic activity

Christopher R. Horne, Tingting Wang, Samuel N. Young, Toby A. Dite et autres

Calmodulin (CaM) serves an essential role in eukaryotic cells as a Ca2+ sensor. Ca2+ binding leads to conformation changes in CaM that enable engagement of a repertoire of enzymes and the regulation of their catalytic activities. Classically, Ca2+-CaM binds to an inhibitory …

au, us, ca (code pays fourni par la source)

Impact of BECLIN1 haploinsufficiency on goblet cell function and susceptibility to colitis

Erinna F. Lee, Juliani Juliani, Sharon H. Tran, Tiffany J. Harris et autres

au (code pays fourni par la source)

Sufficient levels of BECLIN1 are required for intestinal epithelial cell homeostasis and protection against unwanted intestinal inflammation

Juliani Juliani, Sharon H. Tran, Tiffany J. Harris, Sarah L. Ellis et autres

ABSTRACT The prototypical autophagy regulator BECLIN1, orchestrates both autophagic and endocytic trafficking, and its homozygous deletion in the intestinal epithelium leads to intestinal disruption bearing similarities to inflammatory bowel disease (IBD). However, complete loss of BECLIN1 is rare in human disease. To …

au (code pays fourni par la source)

The kinase domain of RIPK3 tunes its scaffolding functions

Shene Chiou, Komal M. Patel, Adele Preaudet, James A. Rickard et autres

ABSTRACT The pro-inflammatory programmed cell death pathway, necroptosis, relies on phosphorylation of the terminal effector, MLKL, by RIPK3. RIPK3-deficient mice or those harboring the kinase-inactivating mutation, RIPK3 K51A , are ostensibly normal in the absence of challenge, indicating that RIPK3 and its …

au (code pays fourni par la source)

PSKH1 kinase activity is differentially modulated via allosteric binding of Ca 2+ sensor proteins

Christopher R. Horne, Toby A. Dite, Samuel N. Young, Lucy J. Mather et autres

Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung, and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, we …

au, us, cn, il, ca, gb, jp (code pays fourni par la source)

DOP109 A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

Aysha Al‐Ani, Jie Pang, Kamal Patel, Samuel N. Young et autres

Abstract Background Dysregulated programmed cell death plays a key role in IBD pathogenesis, with clinical trials exploring anti-necroptotic therapies (1,2). While apoptosis and necroptosis are well-studied in murine colitis models, their prevalence, mechanisms, and therapeutic relevance in human IBD remains unclear. We …

au, us, cn (code pays fourni par la source)

PSKH1 kinase activity is differentially modulated via allosteric binding of Ca 2+ sensor proteins

Christopher R. Horne, Toby A. Dite, Samuel N. Young, Lucy J. Mather et autres

Abstract Protein Serine Kinase H1 (PSKH1) was recently identified as a crucial factor in kidney development and is overexpressed in prostate, lung and kidney cancers. However, little is known about PSKH1 regulatory mechanisms, leading to its classification as a “dark” kinase. Here, …

au, us, gb (code pays fourni par la source)