The IL-4-induced tyrosine phosphorylation of the insulin receptor substrate is dependent on JAK1 expression in human fibrosarcoma cells.
It has been shown that IL-4 induces the tyrosine phosphorylation of JAK1 and JAK3 in the majority of hemopoietic cell types, and JAK2 and TYK2 in several other types. However, the significance of this tyrosine phosphorylation in regulating IL-4 signaling has not been shown. To determine whether JAKs play a role in activating a signal transduction pathway different from the classical JAK/STAT pathway, we analyzed the ability of huIL-4 to stimulate the tyrosine phosphorylation of one of its major cellular substrates, the insulin receptor substrate (IRS). Using human fibrosarcoma cell lines with mutations in JAK1, JAK2, and TYK2, we found that expression of functional JAK1, but not TYK2 or JAK2, is essential for IL-4-induced tyrosine phosphorylation of IRS. We also provide evidence that the IRS pathway is independent of STAT-6, showing that JAK1 is essential for activating a STAT-independent pathway.
Wang
H Y
HY
Immunology Department, Jerome Holland Laboratories, American Red Cross, Rockville, MD 20855, USA.
Zamorano
J
J
Yoerkie
J L
JL
Paul
W E
WE
Keegan
A D
AD
D005354:Fibrosarcoma / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000502:physiology*; D053613:Janus Kinase 1; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D014407:Tumor Cells, Cultured
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1