Tyrosine phosphorylation of JAK-TYK kinases in malignant plasma cell lines growth-stimulated by interleukins 6 and 11.
The pleiotropic cytokine interleukin (IL-6) is a major growth factor for murine plasmacytomas/hybridomas and human myeloma cells. Here we report that IL-6 stimulated different patterns of tyrosine phosphorylation of JAK-TYK kinases in IL-6-responsive murine (B9E and T10D) and human (ANBL-6 and OCI-My4) plasma cell tumor lines. Interestingly, the Stat91 transcription factor essential for interferon signaling mediated by JAK-TYK kinases was significantly tyrosine phosphorylated in response to IL-6 in ANBL-6 cells but not in the other cell lines. We further show that IL-11, a cytokine that signals via the gp130 subunit of the IL-6 receptor, induced similar profiles of JAK-TYK tyrosine phosphorylation as IL-6 in B9E and T10D cells. These results suggest that functionally redundant JAK-TYK kinase cascades triggered through gp130 are involved in the growth regulation of plasma cell neoplasms.
Berger
L C
LC
Division of Cancer Research, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Hawley
T S
TS
Lust
J A
JA
Goldman
S J
SJ
Hawley
R G
RG
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D015151:Immunoblotting; D017370:Interleukin-11 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D051379:Mice; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D010954:Plasmacytoma; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D053634:TYK2 Kinase; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D017370:Interleukin-11; D015850:Interleukin-6; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; C507905:Jak1 protein, mouse; C507926:Jak2 protein, mouse; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse