A serine/threonine kinase p90rsk1 phosphorylates the anti-proliferative protein Tob.
BACKGROUND
tob is a member of a gene family with anti-proliferative function. Over-expression of Tob in NIH3T3 cells results in the suppression of cell proliferation. The growth suppression is hampered by the presence of activated ErbB2 kinase. The molecular mechanisms by which Tob suppresses cell growth and by which ErbB2 abrogates Tob function remain to be elucidated.


RESULTS
We show that Tob is phosphorylated on serines and threonines, but not tyrosines, by a kinase(s) that associates with Tob in the lysates of various cells, including ErbB2-over-expressed cells. We also show that a 95 kDa kinase associates with Tob in vitro. The autophosphorylation activity of this kinase co-chromatographes with Tob-phosphorylating activity, suggesting that the 95 kDa kinase phosphorylates Tob. Among the known kinases with molecular mass around 95 kDa, p90rsk1 associates with Tob in vitro and in vivo, and phosphorylates Tob at least in vitro. Therefore, it is likely that p90rsk1 represents the 95 kDa kinase and is involved in the regulation of Tob function through phosphorylation.


CONCLUSIONS
p90rsk1 associates with and phosphorylates Tob. Because p90rsk1 is activated downstream of receptor tyrosine kinases, we propose that Tob function is at least in part under the control of growth factor-stimulated tyrosine kinases through its phosphorylation by p90rsk1.
Suzuki
T
T
Department of Oncology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Matsuda
S
S
Tsuzuku
J K
JK
Yoshida
Y
Y
Yamamoto
T
T
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490903:Tob1 protein, mouse; D019893:Ribosomal Protein S6 Kinases