The protein kinase mos activates MAP kinase kinase in vitro and stimulates the MAP kinase pathway in mammalian somatic cells in vivo

Abstract

The mos protooncogene encodes a serine/threonine protein kinase that is only expressed at significant levels in germ cells. Recombinant muZE-mos protein (Xenopas mos protooncogene fused in frame to the maltose binding protein of E. coli) activates MAP kinase in cell-free extracts prepared from Xenopus oocytes and eggs. Here we show that malE-mos immunoprecipitates from Xenopus extracts phosphorylate and activate MAP kiiase kinase in vitro, indicating that MOS can function as a MAP kinase kinase kinase. Moreover, ectopic expression of mos in mammalian somatic cells, that lack any endogenous mos protein, triggers the activation of MAP kinase in vivo. These results identify the mos protooncogene as a direct activator of the MAP kinase pathway, with the potential to activate this kinase cascade even in cells where normally there is no expression of mos.

Initiation of Xenopus Oocyte Maturation by Activation of the Mitogen-activated Protein Kinase Cascade

“…4) In the presence of cycloheximide, injection of STE11 protein did not induce activation of MPF or increase in the protein level of Mos or full activation of MAPK (this study). 5) Mos is a MAPKK kinase (23,25). On the other hand, the MAPK cascade may be important for induction and/or accumulation of Mos protein since ectopic expression of CL100 reduced the protein level of Mos (this study), and the activation of the MAPK cascade can induce Mos protein as described above.…”

“…MAPKK and MAPK can be activated downstream of Mos, as injection of Mos protein into oocytes or addition of Mos protein into oocyte extracts rapidly activates MAPKK and MAPK (22)(23)(24). Subsequently, Mos was shown to be a MAPKK kinase, which directly phosphorylates and activates MAPKK (23,25). Not only Mos but also many other agents that can induce MAPK activation (such as insulin, insulin-like growth factor-I, Ras, active Raf, active epidermal growth factor receptor, Trk, and Tpr-Met) can induce oocyte maturation (26 -33).…”

Xenopus H-RasV12 promotes entry into meiotic M phase and cdc2 activation independently of Mos and p42MAPK

“…The progesterone pathway involves the inhibition of PKA activity, which subsequently leads to the synthesis of new specific proteins, required to activate cdc2. One of the maternal mRNA that needs to be translated encodes for Mos (Sagata et al, 1988) that indirectly activates p42 MAPK (Nebreda et al, 1993a;Posada et al, 1993). The requirement of Mos synthesis and p42 MAPK activation for cdc2 activation is controversial.…”

Signaling by dual specificity kinases

“…However, it is worth noting that MKK1/2 can also be activated through a Ras-Raf independent pathway. MKK1/2 can be phosphorylated by other dual speci®city kinase kinase such as cMOS (Nebreda et al, 1993;Shibuya and Rudersman, 1993;Posada et al, 1993) or MEKK1 (Lange-Carter et al, 1993). Phosphorylation of MKK1 by cMOS has been observed only in Xenopus oocytes suggesting cell-type speci®city of MOS-MKK1 interaction.…”