In molecular biology

Molecular biology

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

, ribosomal s6 kinase (rsk) is a family of protein kinase

Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

s involved in signal transduction

Signal transduction

Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...

. 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

Serine/threonine-specific protein kinase

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...

 and are activated by the MAPK/ERK pathway

MAPK/ERK pathway

The MAPK/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 growth factor binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a...

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

Substrates

Rsk is named for ribosomal protein s6

Ribosomal protein s6

Ribosomal protein S6 is a component of the 40S ribosomal subunit and is therefore thought to be involved in regulating translation. Once thought to regulate the translation of 5' terminal oligopyrimidine RNA, this has since been disproven...

, part of the mechanism of translation, but several other substrates have been identified, including other ribosomal proteins. Cytosolic substrates of p90^rsk include protein phosphatase 1

Protein phosphatase 1

Phosphoprotein phosphatase 1 belongs to a certain class of phosphatases known as protein serine/ threonine phosphatases. This type of phosphatase includes metal-dependent protein phosphatases and aspartate-based phosphatases...

; glycogen synthase kinase 3

GSK-3

Glycogen synthase kinase 3 is a serine/threonine protein kinase that mediates the addition of phosphate molecules on certain serine and threonine amino acids in particular cellular substrates...

 (GSK3); L1 CAM

L1 (protein)

L1, also known as L1CAM, is a transmembrane protein; it is a neuronal cell adhesion molecule, member of the L1 protein family, of 200-220 kDa, and involved in axon guidance and cell migration with a strong implication in treatment-resistant cancers....

, a neural cell adhesion molecule; Son of Sevenless

Son of Sevenless

In cell signalling, Son of Sevenless refers to a set of genes encoding guanine nucleotide exchange factors that act on the Ras subfamily of small GTPases.-History and name:...

, the Ras

Ras

Ras is the name given to a family of related proteins found inside cells, including human cells. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells...

 exchange factor; and Myt1

MYT1

Myelin transcription factor 1 is a protein that in humans is encoded by the MYT1 gene.- External links :...

, an inhibitor of cdc2.

p90^rsk also regulates transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s including cAMP response element-binding protein

CREB

CREB is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements , thereby increasing or decreasing the transcription of the downstream genes....

 (CREB); estrogen receptor

Estrogen receptor

Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...

-α (ERα); IκBα/NF-κB; and c-Fos

C-Fos

In the field of molecular biology and Genetics, c-Fos is a protein encoded by the FOS gene.-Structure and function:c-Fos is a cellular proto-oncogene belonging to the immediate early gene family of transcription factors. c-Fos has a leucine-zipper DNA binding domain, and a transactivation domain at...

.

Genomics

p90 Rsk-1

RPS6KA1

HU-1 redirects here. For the helicopter, see UH-1 Iroquois.Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.-Interactions:RPS6KA1 has been shown to interact with YWHAB, MAPK1, IκBα, TOB1 and TSC2....

 is located at 1p.

p90 Rsk-2 is located at Xp22.2

X chromosome

The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...

 and contains 22 exon

Exon

An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

s. Mutations in this gene have been associated with Coffin-Lowry syndrome

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.-History:...

, 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

African clawed frog

The African clawed frog is a species of South African aquatic frog of the genus Xenopus. Its name is derived from the three short claws on each hind foot, which it uses to tear apart its food...

eggs by Erikson and Maller in 1985.