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 Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

. 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 protei ...

and are activated by the

MAPK/ERK pathway The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling ...

. There are two known mammalian homologues of S6 Kinase: S6K1 and S6K2.

Substrates

Both p90 and p70 Rsk phosphorylate

ribosomal protein s6 Ribosomal protein S6 (rpS6 or eS6) is a component of the 40S ribosomal subunit and is therefore involved in translation. Mouse model studies have shown that phosphorylation of eS6 is involved in the regulation of cell size, cell proliferation, and ...

, 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 fou ...

; 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 encod ...

, the

Ras Ras or RAS may refer to: Arts and media * RAS Records Real Authentic Sound, a reggae record label * Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service * Rás 1, an Icelandic radio station * Rás 2, an Icelandic radio stati ...

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 trans ...

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 fu ...

s including

cAMP response element-binding protein CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...

(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 Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkin ...

Genomics

p90 Rsk-1 is located at 1p. p90 Rsk-2 is located at Xp22.2 and contains 22

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s. 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