Jak family of kinases in cancer

Amit Verma, Suman Kambhampati, Simrit Parmar, Leonidas C. Platanias

Research output: Contribution to journalReview article

105 Scopus citations

Abstract

The family of Jak kinases is composed from at least four different tyrosine kinases (Tyk2, Jak1, Jak2, Jak3) that share significant structural homology with each other. The members of this family of kinases associate constitutively with a variety of cytokine and hormone receptors. Upon binding of the specific ligands to their receptors, Jak kinases are rapidly activated and their kinase activities induced, to regulate tyrosine phosphorylation of various effectors and initiate activation of downstream signaling pathways. The discovery of this family of tyrosine kinases dates back in the early 1990s with the cloning of the Tyk-2 tyrosine kinase as a critical element of the Type I interferon signaling pathway. Extensive work over the last few years has provided evidence that Jak kinases play important roles in the generation of responses for interferons, which are cytokines that exhibit important antitumor activities. There is also accumulating evidence that constitutive activation of different Jaks and Stats mediates neoplastic transformation and promotes abnormal cell proliferation in various malignancies. This review summarizes the role of various Jak-kinase dependent pathways in malignancies and discusses the therapeutic implications of the recent advances in the field.

Original languageEnglish (US)
Pages (from-to)423-434
Number of pages12
JournalCancer and Metastasis Reviews
Volume22
Issue number4
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Keywords

  • Cancer
  • Interferons
  • Janus kinases
  • Stat signaling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Verma, A., Kambhampati, S., Parmar, S., & Platanias, L. C. (2003). Jak family of kinases in cancer. Cancer and Metastasis Reviews, 22(4), 423-434. https://doi.org/10.1023/A:1023805715476