Comparative study on the phosphotyrosine motifs of different cytokine receptors involved in STAT5 activation.
Several cytokines and growth factors activate transcription of their target genes via the JAK/STAT signalling pathway. It has been shown that the interaction between SH2 domains of STAT factors and receptor phosphotyrosine residues plays an essential role in the specific recruitment of STATs. For STAT5, however, the importance of receptor tyrosines is still controversial. Using a chimeric receptor system in COS-7 cells, we studied the activation of STAT5 through the interleukin-6 signal transducer gp130. In contrast to previous reports, we did not detect gp130-mediated STAT5 activation. However, STAT5 activation was achieved when tyrosine motifs of other cytokine receptors were fused to the membrane-proximal part of gp130. The comparison of the relative potency of different tyrosine motifs revealed that hydrophobic amino acids, preferentially leucine, in positions +1 and +3, and an aspartate residue in position -1 or -2 with respect to the tyrosine are likely to be required for efficient STAT5 recruitment. In summary, we show here for the first time that phosphotyrosine motifs can confer the ability to activate STAT5 to a heterologous receptor.
May
P
P
Institut für Biochemie der RWTH Aachen, Germany.
Gerhartz
C
C
Heesel
B
B
Welte
T
T
Doppler
W
W
Graeve
L
L
Horn
F
F
Heinrich
P C
PC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D019556:COS Cells; D003001:Cloning, Molecular; D050822:Cytokine Receptor gp130; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008894:Milk Proteins; D009687:Nuclear Proteins; D009842:Oligopeptides; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism; D019000:Phosphotyrosine / Q000737:chemistry*; D018121:Receptors, Cytokine / Q000737:chemistry* / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D015703:Antigens, CD; D015342:DNA Probes; D004268:DNA-Binding Proteins; D000939:Epitopes; D008562:Membrane Glycoproteins; D008894:Milk Proteins; D009687:Nuclear Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D018121:Receptors, Cytokine; D017467:Receptors, Erythropoietin; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D019000:Phosphotyrosine; C085706:FLAG peptide