Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11.
Interleukin-11 is a stromal derived cytokine important in hematopoiesis. IL-11 intracellular signaling travels through cytoplasmic kinases of the Janus family. How JAKs accomplish the multiple functions of IL-11 has not been determined and until recently only a few associated downstream proteins have been identified. We present evidence here for the IL-11 induced association of PP2A, P13K, and Yes to JAK2. Reciprocal immunoprecipitations support the mutual involvement of these signaling components in IL-11 mediated signal transduction. This novel finding of JAK2/PP2A binding and release may have relevance to many serine/threonine regulated mechanisms such as P13K, 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.
Fuhrer
D K
DK
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202, USA.
Yang
Y C
YC
D016475:3T3 Cells; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase; D015151:Immunoblotting; D017370:Interleukin-11 / Q000494:pharmacology*; D053614:Janus Kinase 2; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000302:isolation & purification / Q000378:metabolism*; D019000:Phosphotyrosine / Q000032:analysis; D011505:Protein-Tyrosine Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051575:Proto-Oncogene Proteins c-yes; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases
D017370:Interleukin-11; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D005982:Glutathione Transferase; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D051575:Proto-Oncogene Proteins c-yes; C496639:Yes1 protein, mouse; D019061:src-Family Kinases; D010749:Phosphoprotein Phosphatases