Recent studies indicate that kinase suppressor of Ras (KSR)is a scaffold protein for the Ras/Raf/MEK/ERK signaling cascade in mammals. KSR1 translocates from the cytoplasm to the cell surface in response to growth factor treatment and that this process is regulated by CDC25C-associated kinase-1 (CTAK1; OMIM 602678). CTAK1 constitutively associates with mammalian KSR1 and phosphorylates ser392 to confer 14-3-3 binding and cytoplasmic sequestration of KSR1 in unstimulated cells. In response to signal activation, the phosphorylation state of ser392 is reduced, allowing the KSR1 complex to colocalize with activated RAS and RAF1 (OMIM 164760) at the plasma membrane, thereby facilitating the phosphorylation reactions required for the activation of MEK and MAPK.
General function
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Cellular localization
Cytoplasmic, Plasma membrane
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Ovarian function
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Expression regulated by
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Ovarian localization
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Giblett SM, et al 2002 reported the expression of kinase suppressor of ras in the normal adult and embryonic mouse.
To help determine the in vivo function of KSR, the authors have examined the tissue-specific distribution of this protein in the embryonic and adult mouse using a rat monoclonal antibody raised against the mouse protein. Western blot analysis indicates that the protein is expressed at highest levels in the adult brain. It is also expressed at low levels in bladder, ovary, testis, and lung, but the protein is not detectable in any other adult tissue. However, reverse transcription-PCR analysis shows that Ksr transcripts are detected in all adult tissues except the liver. A variant containing a differentially spliced exon in the CA4 domain is observed in brain, cerebellum, ovary, and intestine. The protein is also expressed throughout the E6.5 embryo and at high levels in the neuroepithelium of the E10.5 embryo. At this embryonic stage, expression is also detected at lower levels in the limb and tail buds as well as in the myocardium.