Plant growth and development are coordinately orchestrated by environmental cues and phytohormones. Light acts as a key environmental factor for fundamental plant growth and physiology through photosensory phytochromes and underlying molecular mechanisms. Although phytochromes are known to possess serine/threonine protein kinase activities, whether they trigger a signal transduction pathway via an intracellular protein kinase network remains unknown. In analyses of mitogen-activated protein kinase kinase (MAPKK, also called MKK) mutants, the mkk3 mutant has shown both a hypersensitive response in plant hormone gibberellin (GA) and a less sensitive response in red light signaling. Surprisingly, light-induced MAPK activation in wild-type (WT) seedlings and constitutive MAPK phosphorylation in dark-grown mkk3 mutant seedlings have also been found, respectively. Therefore, this study suggests that MKK3 acts in negative regulation in darkness and in light-induced MAPK activation during dark-light transition.
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http://dx.doi.org/10.14348/molcells.2015.0055 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
January 2025
Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan, China.
Langerhans cell histiocytosis (LCH) is characterized genetically by diverse gene mutations of the mitogen-activated protein kinase signaling cascade. BRAFN486_T491delinsK mutation is a rare mutation that involves the β2-αC ring domain, causing activation of the mitogen-activated protein kinase pathway, and is predicted to be resistant to the chemotherapy and BRAFV600E inhibitor in adult LCH cases. Here, we report a childhood LCH case with this novel BRAF mutation and had a good response to conventional chemotherapy.
View Article and Find Full Text PDFJ Neurochem
January 2025
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Severe trauma frequently leads to nerve damage. Peripheral nerves possess a degree of regenerative ability, and actively promoting their recovery can help restore the sensory and functional capacities of tissues. The neuropeptide calcitonin gene-related peptide (CGRP) is believed to regulate the repair of injured peripheral nerves, with neuronal transient receptor potential vanilloid type 1 (TRPV1) potentially serving as a crucial upstream factor.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Opthalmology, Chongqing Hechuan District People's Hospital, Chongqing, China.
Background: Bushen-Huoxue-Mingmu-Formula (MMF) has achieved definite clinical efficacy. However, its mechanism is still unclear.
Objective: Investigating the molecular mechanism of MMF to protect retinal ganglion cells (RGCs).
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