COMPLEX-FORMATION OF JAK2 WITH PP2A, P13K, AND YES IN RESPONSE TO THEHEMATOPOIETIC CYTOKINE INTERLEUKIN-11

Interleukin-11 is a stromal derived cytokine important in hematopoiesi s. IL-11 intracellular signaling travels through cytoplasmic kinases o f the Janus family. How JAKs accomplish the multiple functions of IL-1 1 has not been determined and until recently only a few associated dow nstream proteins have been identified. We present evidence here for th e IL-11 induced association of PP2A, PI3K, and Yes to JAK2. Reciprocal immunoprecipitations support the mutual involvement of these signalin g components in IL-11 mediated signal transduction. This novel finding of JAK2/PP2A binding and release may have relevance to many serine/th reonine regulated mechanisms such as PI3K, Stat, and MAPK activation. These associations support a model of JAK2 as a protein kinase docking protein of IL-11 signal transduction that may be applicable to other gp130 and JAK signal transduction systems. (C) 1996 Academic Press. In c.