KSR1
Scaffolding protein that is part of a multiprotein signaling complex. Promotes phosphorylation of Raf family members and activation of downstream MAP kinases. Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP.
Full Name
Kinase Suppressor Of Ras 1
Function
Part of a multiprotein signaling complex which promotes phosphorylation of Raf family members and activation of downstream MAP kinases (By similarity).
Independently of its kinase activity, acts as MAP2K1/MEK1 and MAP2K2/MEK2-dependent allosteric activator of BRAF; upon binding to MAP2K1/MEK1 or MAP2K2/MEK2, dimerizes with BRAF and promotes BRAF-mediated phosphorylation of MAP2K1/MEK1 and/or MAP2K2/MEK2 (PubMed:29433126).
Promotes activation of MAPK1 and/or MAPK3, both in response to EGF and to cAMP (By similarity).
Its kinase activity is unsure (By similarity).
Some protein kinase activity has been detected in vitro, however the physiological relevance of this activity is unknown (By similarity).
Biological Process
cAMP-mediated signalingISS:UniProtKB
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Ras protein signal transductionISS:UniProtKB
Regulation of cell population proliferationISS:UniProtKB
Regulation of MAP kinase activityISS:UniProtKB
Signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Cellular Location
Cytoplasm
Membrane 1 Publication
Cell membrane
Cell projection, ruffle membrane
Endoplasmic reticulum membrane
In unstimulated cells, where the phosphorylated form is bound to a 14-3-3 protein, sequestration in the cytoplasm occurs. Following growth factor treatment, the protein is free for membrane translocation, and it moves from the cytoplasm to the cell periphery.
PTM
Phosphorylated on Ser-311 and, to a higher extent, on Ser-406 by MARK3. Dephosphorylated on Ser-406 by PPP2CA. In resting cells, phosphorylated KSR1 is cytoplasmic and in stimulated cells, dephosphorylated KSR1 is membrane-associated. Phosphorylated by PKA at Ser-888. Phosphorylation at Ser-888 is required for cAMP-dependent activation of MAPK1 and/or MAPK3 (By similarity).
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