Open AccessA hypothalamic pathway for Augmentor α–controlled body weight regulation
Author(s) -
Mansoor Ahmed,
Navjot Kaur,
Qi Cheng,
Marya Shanabrough,
Evgenii Tretiakov,
Tibor Harkany,
Tamas L. Horváth,
Joseph Schlessinger
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2200476119
Subject(s) - biology , phenotype , mutant , knockout mouse , receptor , microbiology and biotechnology , energy homeostasis , receptor tyrosine kinase , hypothalamus , endocrinology , medicine , signal transduction , genetics , gene
Significance The receptor tyrosine kinase Alk was originally discovered as an oncogenic fusion protein generated in anaplastic large cell lymphoma. A variety of oncogenic Alk fusion proteins were subsequently identified as key drivers of subsets of different cancers, including non-small cell lung cancer patients, large B cell lymphomas, and inflammatory myofibroblast tumors. In addition, activating oncogenic somatic mutations were identified in populations of pediatric neuroblastoma patients. Crizotininb, lorlatinib, and other drugs that inhibit the tyrosine kinase activity of Alk were successfully applied for the treatment of patients harboring oncogenic Alk mutants. In this report, we present experiments demonstrating that the physiological ligands of Alk function in the hypothalamus to control body weight, offering new therapeutic treatments for metabolic diseases and cancer.