The family of ribosomal S6 kinases (Rsks), designated Rsk-1, Rsk-2 and Rsk-3, have been implicated as important signaling intermediates in response to a broad range of ligand-activated receptor tyrosine kinases. A unique feature common to the three members of the Rsk family is that each possesses two non-identical complete kinase catalytic domains. A related S6 kinase, p70 S6 kinase, functions to phosphorylate the S6 protein on ribosomal 40S subunits. p70 S6 kinase b shares high sequence homology with p70 S6 kinase, except in the carboxy terminus where it contains a proline-rich domain that may be involved in SH3 domain containing protein interactions. MSK1 (also designated RLPK) is related to Rsk and p70 S6 kinase family members and is thought to be structurally similar to Rsk family members, but it may be regulated by distinct mechanisms.
Background References
1. Malvi P et al. HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B. Cell Rep Med. 2023 Nov
2. Ning B et al. MSK1 downregulation is involved in inflammatory responses following subarachnoid hemorrhage in rats. Exp Ther Med. 2021 Apr
Sequence Similarity
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
Tissue Specificity
Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.
Post-translational Modification
Ser-376 and Thr-581 phosphorylation is required for kinase activity. Ser-376 and Ser-212 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-360, Thr-581 and Thr-700 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha. Autophosphorylated at Ser-750, Ser-752 and Ser-758 by the N-terminal kinase domain.; Ubiquitinated.
Immunocytochemistry analysis of HEK-293 cells treated with or without 200nM PMA for 30 minutes labeling Phospho-MSK1 (S376) with Rabbit anti-Phospho-MSK1 (S376) antibody (ET1611-17) at 1/100 dilution.
Cells were fixed in 4% paraformaldehyde for 20 minutes at room temperature, permeabilized with 0.1% Triton X-100 in PBS for 5 minutes at room temperature, then blocked with 1% BSA in 10% negative goat serum for 1 hour at room temperature. Cells were then incubated with Rabbit anti-Phospho-MSK1 (S376) antibody (ET1611-17) at 1/100 dilution in 1% BSA in PBST overnight at 4 ℃. Goat Anti-Rabbit IgG H&L (iFluor™ 488, HA1121) was used as the secondary antibody at 1/1,000 dilution. PBS instead of the primary antibody was used as the secondary antibody only control. Nuclear DNA was labelled in blue with DAPI.
Beta tubulin (M1305-2, red) was stained at 1/100 dilution overnight at +4℃. Goat Anti-Mouse IgG H&L (iFluor™ 594, HA1126) was used as the secondary antibody at 1/1,000 dilution.
Immunohistochemical analysis of paraffin-embedded human colon tissue using anti-Phospho-MSK1 (S376) antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 9.0) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1611-17, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded rat bladder tissue using anti-Phospho-MSK1 (S376) antibody. The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH 6.0) (high pressure) for 2 minutes. The tissues were blocked in 1% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1611-17, 1/400) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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