Receptor serine/threonine kinase (RSTK) family

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Receptor serine/threonine kinases (RTSK), EC 2.7.11.30, respond to particular cytokines, the transforming growth factor β (TGFβ) and bone morphogenetic protein (BMP) families, and may be divided into two subfamilies on the basis of structural similarities. Agonist binding initiates formation of a cell-surface complex of type I and type II RSTK, possibly heterotetrameric, where where both subunits express serine/threonine kinase activity. The type I receptor serine/threonine kinases (ENSFM00250000000213) are also known as activin receptors or activin receptor-like kinases, ALKs, for which a systematic nomenclature has been proposed (ALK1-7). The type II protein phosphorylates the kinase domain of the type I partner (sometimes referred to as the signal propagating subunit), causing displacement of the protein partners, such as the FKBP12 FK506-binding protein FKBP1A (P62942) and allowing the binding and phosphorylation of particular members of the Smad family. These migrate to the nucleus and act as complexes to regulate gene transcription. Type III receptors, sometimes called co-receptors or accessory proteins, regulate the signalling of the receptor complex, in either enhancing (for example, presenting the ligand to the receptor) or inhibitory manners. TGFβ family ligand signalling may be inhibited by endogenous proteins, such as follistatin (FST, P19883), which binds and neutralizes activins to prevent activation of the target receptors.

Endogenous agonists, approximately 30 in man, are often described as paracrine messengers acting close to the source of production. They are characterized by six conserved cysteine residues and are divided into two subfamilies on the basis of sequence comparison and signalling pathways activated, the TGFβ/activin/nodal subfamily and the BMP/GDF (growth/differentiation factor)/MIS (Müllerian inhibiting substance) subfamily. Ligands active at RSTKs appear to be generated as large precursors which undergo complex maturation processes [2]. Some are known to form disulphide-linked homo- and/or heterodimeric complexes. Thus, inhibins are α subunits linked to a variety of β chains, while activins are combinations of β subunits.

Type I receptor serine/threonine kinases

Overview

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The type I receptor serine/threonine kinases (ENSFM00250000000213) are also known as activin receptors or activin receptor-like kinases, ALKs, for which a systematic nomenclature has been proposed (ALK1-7).

Receptors

ALK1 (activin A receptor type II-like 1) Show summary » More detailed page

ALK2 (activin A receptor, type I) Show summary » More detailed page

BMPR1A (bone morphogenetic protein receptor, type IA) Show summary » More detailed page

ALK4 (activin A receptor, type IB) Show summary » More detailed page

TGFBR1 (transforming growth factor, beta receptor 1) Show summary » More detailed page

BMPR1B (bone morphogenetic protein receptor, type IB) Show summary » More detailed page

ALK7 (activin A receptor, type IC) Show summary » More detailed page

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Type II receptor serine/threonine kinases

Receptors

ActR2 (activin A receptor, type IIA) Show summary » More detailed page

ActR2B (activin A receptor, type IIB) Show summary » More detailed page

MISR2 (anti-Mullerian hormone receptor, type II) Show summary » More detailed page

BMPR2 (bone morphogenetic protein receptor, type II (serine/threonine kinase)) Show summary » More detailed page

TGFBR2 (transforming growth factor, beta receptor II (70/80kDa)) Show summary » More detailed page

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Type III receptor serine/threonine kinases

Receptors

TGFBR3 (transforming growth factor, beta receptor III) Show summary » More detailed page

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RSTK functional heteromers

Receptors

Transforming growth factor β receptor Show summary »

Bone morphogenetic protein receptors Show summary »

Growth/differentiation factor receptors Show summary »

Activin receptors Show summary »

Anti-Müllerian hormone receptors Show summary »

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Further reading

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References

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