The ERK MAP kinase pathway mediates induction of SGK (serum- and glucocorticoid-inducible kinase) by growth factors.
BACKGROUND
The ERK MAP kinase pathway plays a pivotal role in growth factor-induced gene expression. However, genes whose expression is induced by the ERK pathway are not fully defined.


RESULTS
We have identified SGK (serum- and glucocorticoid-inducible kinase) as an ERK-inducible gene by the subtractive screening of Raf-inducible genes. SGK is known to be similar in primary structure to AKT/PKB, PKC and PKA. Treatment of quiescent NIH-3T3 cells with FGF, PDGF or TPA, which induced the sustained activation of ERKs, resulted in the strong induction of SGK, whereas treatment with EGF, which induced the transient activation of ERKs, did not induce a strong expression of SGK. The induction of SGK was blocked by pre-treatment with a specific MEK inhibitor U0126, and expression of constitutively active MEK was able to induce SGK. Treatment with cycloheximide or vanadate prolonged the increased expression of SGK by FGF, concomitant with a more prolonged activation of ERKs.


CONCLUSIONS
Growth factor-induced activation of the ERK MAP kinase pathway is necessary and sufficient for the induction of SGK.
Department of Biophysics, Graduate School of Science, and Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
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Mizuno
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Nishida
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000235:genetics; D004790:Enzyme Induction / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006133:Growth Substances / Q000502:physiology*; D017874:Immediate-Early Proteins; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
D006133:Growth Substances; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D000099184:Serum-Glucocorticoid Regulated Kinases; C093328:Plk3 protein, mouse