Mechanisms of cytokine signal transduction: IL-2, IL-4 and prolactin as hematopoietin receptor models.
Cytokines, hormones and hematopoietic growth factors transduce biological signals across the cell membrane via a highly conserved family of single membrane-spanning receptors. The intracellular signal transducing machinery responsible for mediating these responses has remained largely unknown. However, recent identification of a homologous class of tyrosine kinases, Janus Kinases (JAKs), and a related family of transcription 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 research efforts within the field of cytokine signaling have now shifted to understanding how these molecules are activated by hematopoietic receptors, positively and negatively regulated by kinases and phosphatases, and how they impact on gene transcription to ultimately coordinate cell homeostasis, proliferation and differentiation. This article will review some of our results identifying the involvement of JAKs, STATs, and secondary effector molecules activated following engagement of hematopoietic receptors for IL-2, IL-4, and prolactin. Here, we provide evidence for the ingenious ability of cytokine receptors to selectively recruit and activate these proteins among a repertoire of possible alternative biochemical messengers as a means to affect unique and general cell responses.
Kirken
R A
RA
Intramural Research Support Program, SAIC-Frederick, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702-1201, USA. kirken@mail.ncifcrf.gov
Evans
G A
GA
Duhé
R J
RJ
DaSilva
L
L
Malabarba
M G
MG
Erwin
R A
RA
Farrar
W L
WL
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008954:Models, Biological; D011388:Prolactin / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D018121:Receptors, Cytokine / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology
D016207:Cytokines; D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D007376:Interleukin-2; D018121:Receptors, Cytokine; D015534:Trans-Activators; D015847:Interleukin-4; D011388:Prolactin; D011505:Protein-Tyrosine Kinases