MECHANISMS OF CYTOKINE SIGNAL-TRANSDUCTION - IL-2, IL-4 AND PROLACTINAS HEMATOPOIETIN RECEPTOR MODELS

Cytokines, hormones and hematopoietic growth factors transduce biologi cal signals across the cell membrane via a highly conserved family of single membrane-spanning receptors. The intracellular signal transduci ng machinery responsible for mediating these responses has remained la rgely unknown. However, recent identification of a homologous class of tyrosine kinases, Janus Kinases (JAKs), and a related family of trans cription factors, signal transducers and activators of transcription ( STATs), has shed new light on the molecular mechanisms responsible for mediating hematopoietin signaling and immune response. Current resear ch efforts within the field of cytokine signaling have now shifted to understanding how these molecules are activated by hematopoietic recep tors, positively and negatively regulated by kinases and phosphatases, and how they impact on gene transcription to ultimately coordinate ce ll homeostasis, proliferation and differentiation. This article will r eview some of our results identifying the involvement of JAKs, STATs, and secondary effector molecules activated following engagement of hem atopoietic receptors for IL-2, IL-4, and prolactin. Here, we provide e vidence for the ingenious ability of cytokine receptors to selectively recruit and activate these proteins among a repertoire of possible al ternative biochemical messengers as a means to affect unique and gener al cell responses. (C) 1998 Elsevier Science B.V. All rights reserved.