COMPARATIVE-STUDY ON THE PHOSPHOTYROSINE MOTIFS OF DIFFERENT CYTOKINERECEPTORS INVOLVED IN STAT5 ACTIVATION

Several cytokines and growth factors activate transcription of their t arget genes via the JAK/STAT signalling pathway, It has been shown tha t the interaction between SH2 domains of STAT factors and receptor pho sphotyrosine residues plays an essential role in the specific recruitm ent of STATs, For STAT5, however, the importance of receptor tyrosines is still controversial, Using a chimeric receptor system in COS-7 cel ls, we studied the activation of STAT5 through the interleukin-6 signa l transducer gp130. In contrast to previous reports, we did not detect gp130-mediated STATS activation. However, STATS activation was achiev ed when tyrosine motifs of other cytokine receptors were fused to the membrane-proximal part of gp130, The comparison of the relative potenc y of different tyrosine motifs revealed that hydrophobic amino acids, preferentially leucine, in positions +1 and +3, and an aspartate resid ue in position -1 or -2 with respect to the tyrosine are likely to be required for efficient STATS recruitment, In summary, me show here for the first time that phosphotyrosine motifs can confer the ability to activate STATS to a heterologous receptor.