kinase suppressor of ras-1 (KSR, KSR1)

Function

• location-regulated scaffold connecting MEK to RAF
• promotes MEK & RAF phosphorylation & activity via assembly of activated signaling complex
• by itself, it has no kinase activity
• interacts with HSP90, 14-3-3, CDC37, MEK, MARK3, PPP2R1A & PPP2CA.
• interacts with RAF & ERK Ras-dependent)
• phosphorylated KSR1 binds 14-3-3 & sequesters in cytoplasm
• phosphorylated on Ser-309 & Ser-404 by MARK3
• dephosphorylated on Ser-404 by PPP2CA
• binding of 14-3-3 proteins to phosphorylated KSR1 prevents the membrane localization
• interacts with isoform 1 of VRK2

Structure

• belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
• contains 1 phorbol-ester/DAG-type Zn+2 finger
• contains 1 protein kinase domain

Compartment

• cytoplasmic
• membrane-associated, endoplasmic reticulum membrane
• in resting cells, phosphorylated KSR1 is cytoplasmic
• in stimulated cells, dephosphorylated KSR1 is membrane-associated

Alternative splicing

named isoforms=3

More general terms

• phosphoprotein
• zinc finger protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8844
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8844
• OMIM: https://mirror.omim.org/entry/601132
• UniProt: http://www.uniprot.org/uniprot/Q8IVT5.html