Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development.

ABSTRACT: Mammary gland development during pregnancy is controlled by lactogenic hormones via the JAK2-STAT5 pathway. Gene deletion studies in mice have revealed the crucial roles of both STAT5A and STAT5B in establishing the genetic programs necessary for the development of mammary epithelium and successful lactation. Several hundred single nucleotide polymorphisms (SNPs) have been identified in human STAT5B, although their pathophysiological significance remains largely unknown. The SH2 domain is vital for STAT5B activation, and this study focuses on the impact of two specific missense mutations identified in T cell leukemias, the substitution of tyrosine 665 with either phenylalanine (Y665F) or histidine (Y665H). By introducing these human mutations into the mouse genome, we uncovered distinct an

SUBMITTER: Lee HK 

PROVIDER: S-EPMC11958444 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature