KSR1 (kinase suppressor of ras 1)
2011-02-01 Mario Fernandez , Robert Lewis AffiliationEppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE 68198, USA
DNA/RNA
KSR1 contains 17 exons, 154426 base pairs.
Description
The KSR1 gene was discovered in D. melanogaster and is highly conserved along the evolutionary tree through H. sapiens.
Transcription
Transcription can produce two different mRNA transcripts. The KSR1 is expressed in the thymus, bone marrow, brain, heart, kidney, lung, liver, pancreas, mammary gland, ovary, testis and muscle.
Pseudogene
No known pseudogenes.
Proteins
Note
Belongs to the KSR family of proteins.
The KSR1 protein contains five conserved areas (CA). The CA1 region is unique to KSR1 protein; the CA2 region is a proline-rich region; the CA3 region is implicated in the Ras-induced plasma membrane localization; the CA4 region is a serine/threonine rich region and contains the MAPK docking site (FXFP); and the putative kinase domain (CA5), which contains an amino acid variation in subdomain II that suggests that this protein is catalytically inert. The KSR1 protein is composed of 921 amino acids.
Description
The KSR1 protein is 921 kDa. There have been 15 phosphorylation sites identified.
Expression
Brain, kidney, lung, pancreas, ovaries, testis, breast.
Localisation
Sequestered in the cytoplasm in quiescents cells. Upon stimulation, KSR1 protein localizes to the plasma membrane.
Function
Acts as a scaffold for the Raf/MEK/ERK kinase cascade.
Homology
R. norvegicus KSR1 (91.85%), M. musculus KSR1 (91.3%), C. familians KSR1 (93.62%), G. gallus KSR1 (76.39%), D. reno KSR1 (67.85%), D. Melanogaster KSR (41.06%), C. elegans KSR1 (35.37%), X. laevis KSR1 (76.06%).
Mutations
Note
There have been no prominent germinal or somatic mutations identified.
Implicated in
Entity name
Cancer
Note
KSR1 has not been found to be upregulated or downregulated in tumors. However, studies in KSR1 knockout mice showed that the mice were less susceptible to papilloma virus driven tumors, indicating that KSR1 is required for Ras-mediated oncogenesis.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19114553 | 2009 | Ras subcellular localization defines extracellular signal-regulated kinase 1 and 2 substrate specificity through distinct utilization of scaffold proteins. | Casar B et al |
| 18332145 | 2008 | IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. | Chen C et al |
| 17056543 | 2006 | The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis. | Fusello AM et al |
| 12133899 | 2002 | Expression of kinase suppressor of Ras in the normal adult and embryonic mouse. | Giblett SM et al |
| 19139278 | 2009 | The mitogen-activated protein kinase scaffold KSR1 is required for recruitment of extracellular signal-regulated kinase to the immunological synapse. | Giurisato E et al |
| 15899786 | 2005 | Expression of kinase suppressor of Ras1 enhances cisplatin-induced extracellular signal-regulated kinase activation and cisplatin sensitivity. | Kim M et al |
| 8521514 | 1995 | The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated signaling in C. elegans. | Kornfeld K et al |
| 16107706 | 2005 | The molecular scaffold kinase suppressor of Ras 1 (KSR1) regulates adipogenesis. | Kortum RL et al |
| 16507997 | 2006 | The molecular scaffold kinase suppressor of Ras 1 is a modifier of RasV12-induced and replicative senescence. | Kortum RL et al |
| 15121859 | 2004 | The molecular scaffold KSR1 regulates the proliferative and oncogenic potential of cells. | Kortum RL et al |
| 15240686 | 2004 | Kinase suppressor of Ras couples Ras to the ERK cascade during T cell development. | Laurent MN et al |
| 12874031 | 2003 | Deficiency of kinase suppressor of Ras1 prevents oncogenic ras signaling in mice. | Lozano J et al |
| 17613518 | 2007 | Caspase-dependent cleavage disrupts the ERK cascade scaffolding function of KSR1. | McKay MM et al |
| 19541618 | 2009 | Signaling dynamics of the KSR1 scaffold complex. | McKay MM et al |
| 9371754 | 1997 | KSR stimulates Raf-1 activity in a kinase-independent manner. | Michaud NR et al |
| 10891492 | 2000 | Identification of B-KSR1, a novel brain-specific isoform of KSR1 that functions in neuronal signaling. | Müller J et al |
| 11741534 | 2001 | C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1. | Müller J et al |
| 11940661 | 2002 | Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. | Nguyen A et al |
| 12932319 | 2003 | Protein phosphatase 2A positively regulates Ras signaling by dephosphorylating KSR1 and Raf-1 on critical 14-3-3 binding sites. | Ory S et al |
| 19727074 | 2009 | A dimerization-dependent mechanism drives RAF catalytic activation. | Rajakulendran T et al |
| 19147494 | 2009 | KSR1 is required for cell cycle reinitiation following DNA damage. | Razidlo GL et al |
| 17174095 | 2007 | CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase activation. | Ritt DA et al |
| 11850406 | 2002 | KSR is a scaffold required for activation of the ERK/MAPK module. | Roy F et al |
| 15684389 | 2005 | Nm23-H1 metastasis suppressor expression level influences the binding properties, stability, and function of the kinase suppressor of Ras1 (KSR1) Erk scaffold in breast carcinoma cells. | Salerno M et al |
| 8521513 | 1995 | The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in Ras-mediated signal transduction. | Sundaram M et al |
| 8946910 | 1996 | KSR modulates signal propagation within the MAPK cascade. | Therrien M et al |
| 12960962 | 2003 | Pharmacologic inactivation of kinase suppressor of ras-1 abrogates Ras-mediated pancreatic cancer. | Xing HR et al |
| 15520859 | 2004 | Kinase suppressor of Ras-1 protects intestinal epithelium from cytokine-mediated apoptosis during inflammation. | Yan F et al |
Other Information
Locus ID:
NCBI: 8844
MIM: 601132
HGNC: 6465
Ensembl: ENSG00000141068
Variants:
dbSNP: 8844
ClinVar: 8844
TCGA: ENSG00000141068
COSMIC: KSR1
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36493900 | 2023 | SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity. | 2 |
| 37511580 | 2023 | Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells. | 0 |
| 37972068 | 2023 | SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status. | 2 |
| 36493900 | 2023 | SHP2 inhibition mitigates adaptive resistance to MEK inhibitors in KRAS-mutant gastric cancer through the suppression of KSR1 activity. | 2 |
| 37511580 | 2023 | Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells. | 0 |
| 37972068 | 2023 | SOS1 and KSR1 modulate MEK inhibitor responsiveness to target resistant cell populations based on PI3K and KRAS mutation status. | 2 |
| 33461174 | 2021 | Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways. | 6 |
| 33461174 | 2021 | Praja2 suppresses the growth of gastric cancer by ubiquitylation of KSR1 and inhibiting MEK-ERK signal pathways. | 6 |
| 30917119 | 2019 | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. | 5 |
| 30917119 | 2019 | Kinase suppressor of Ras 1 and Exo70 promote fatty acid-stimulated neurotensin secretion through ERK1/2 signaling. | 5 |
| 29433126 | 2018 | MEK drives BRAF activation through allosteric control of KSR proteins. | 68 |
| 29596465 | 2018 | Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor development in a mouse model of RAS-driven pancreatic cancer. | 2 |
| 29980571 | 2018 | Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer. | 17 |
| 29433126 | 2018 | MEK drives BRAF activation through allosteric control of KSR proteins. | 68 |
| 29596465 | 2018 | Homozygous KSR1 deletion attenuates morbidity but does not prevent tumor development in a mouse model of RAS-driven pancreatic cancer. | 2 |
Citation
Mario Fernandez ; Robert Lewis
KSR1 (kinase suppressor of ras 1)
Atlas Genet Cytogenet Oncol Haematol. 2011-02-01
Online version: http://atlasgeneticsoncology.org/gene/41107/ksr1
