The two faces of Janus kinases and their respective STATs in mammary gland development and cancer

Kay Uwe Wagner, Jeffrey Schmidt

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Since its discovery as just another kinase more than twenty years ago, the family of JAK tyrosine kinases and their respective Signal Transducers and Activators of Transcription (STATs) has been a center of attention in the areas of signal transduction, development, and cancer. The subsequent designation of JAKs as Janus kinases after the mythical two-faced Roman God of the doorways accurately portrays the analogous and sometimes contrasting molecular and biological characteristics of these tyrosine kinases. The two faces of JAKs are their structurally similar kinase and pseudo-kinase domains. As essential parts of various transmembrane receptor complexes, these tyrosine kinases function at cellular gateways and relay signals from growth factors to their respective intracellular targets. The multifaceted nature of JAKs becomes evident from their ability to activate specific STATs during distinct phases of normal mammary gland development. Studies in breast cancer cells and genetically engineered mouse models also show that JAK/STAT signaling possesses a two-faced role during breast cancer initiation and progression. This review will highlight recent findings about important biological functions of JAKs and STATs during normal mammogenesis, with particular emphasis on the Jak2/Stat5 pathway as well as Jak1/2/Stat3 signaling complexes. In addition, we will discuss how the importance of these signaling networks changes during carcinogenesis. With JAK inhibitors currently under development to treat myeloproliferative disorders, determining the essential functions of JAKs at particular stages of disease initiation and progression is of critical importance to predict the efficacy of these agents for targeted therapies against breast cancer.

Original languageEnglish (US)
Article number32
JournalJournal of Carcinogenesis
Volume10
DOIs
StatePublished - Dec 1 2011

Fingerprint

Janus Kinases
Human Mammary Glands
Transducers
Breast Neoplasms
Phosphotransferases
Protein-Tyrosine Kinases
Myeloproliferative Disorders
Receptor Protein-Tyrosine Kinases
Disease Progression
Signal Transduction
Intercellular Signaling Peptides and Proteins
Carcinogenesis
Neoplasms

Keywords

  • Breast cancer
  • Janus kinase
  • mammary gland
  • protein-tyrosine kinase
  • signal transducers and activators of transcription
  • signal transduction
  • transcription factors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Health, Toxicology and Mutagenesis

Cite this

The two faces of Janus kinases and their respective STATs in mammary gland development and cancer. / Wagner, Kay Uwe; Schmidt, Jeffrey.

In: Journal of Carcinogenesis, Vol. 10, 32, 01.12.2011.

Research output: Contribution to journalArticle

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