molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...

, ribosomal s6 kinase (rsk) is a family of

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

s involved in signal transduction. There are two subfamilies of rsk, p90^rsk, also known as MAPK-activated protein kinase-1 (MAPKAP-K1), and p70^rsk, also known as S6-H1 Kinase or simply S6 Kinase. There are three variants of p90^rsk in humans, rsk 1-3. Rsks are

serine/threonine kinases A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human pr ...

and are activated by the MAPK/ERK pathway. There are two known mammalian homologues of S6 Kinase: S6K1 and S6K2.

Substrates

Both p90 and p70 Rsk phosphorylate ribosomal protein s6, part of the translational machinery, but several other substrates have been identified, including other ribosomal proteins. Cytosolic substrates of p90^rsk include

protein phosphatase 1 Protein phosphatase 1 (PP1) belongs to a certain class of phosphatases known as protein serine/threonine phosphatases. This type of phosphatase includes metal-dependent protein phosphatases (PPMs) and aspartate-based phosphatases. PP1 has been fo ...

; glycogen synthase kinase 3 (GSK3); L1 CAM, a neural cell adhesion molecule;

Son of Sevenless In cell signalling, ''Son of Sevenless'' (''SOS'') refers to a set of genes encoding guanine nucleotide exchange factors that act on the Ras subfamily of small GTPases. History and name The gene was so named because the Sos protein that it enco ...

, the Ras exchange factor; and Myt1, an inhibitor of

cdc2 Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in th ...

. RSK phosphorylation of SOS1 (

) at Serines 1134 and 1161 creates

14-3-3 14-3-3 proteins are a family of conserved regulatory molecules that are expressed in all eukaryotic cells. 14-3-3 proteins have the ability to bind a multitude of functionally diverse signaling proteins, including kinases, phosphatases, and tran ...

docking site. This interaction of phospho SOS1 and

negatively regulates Ras-MAPK pathway. p90^rsk also regulates

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s including cAMP response element-binding protein (CREB);

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

-α (ERα);

IκBα IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. IκBα inhibits NF-κB by masking the nuclear lo ...

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

; and c-Fos.

Genomics

p90 Rsk-1 is located at 1p. p90 Rsk-2 is located at Xp22.2 and contains 22 exons. Mutations in this gene have been associated with

Coffin–Lowry syndrome Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities. ...

, a disease characterised by severe psychomotor retardation and other developmental abnormalities. p90 Rsk-3 is located at 6q27.

Proteomics

The main distinguishing feature between p90^rsk and p70^rsk is that the 90 kDa family contain two non-identical kinase domains, while the 70 kDa family contain only one kinase domain.

Research history

Rsk was first identified in ''

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws ...

'' eggs by Erikson and Maller in 1985.

References

External links

* * {{Serine/threonine-specific protein kinases Proteins Signal transduction