Kinase Group TK

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Kinase Classification: Tyrosine Kinase (TK) Group

This group phosphorylates almost exclusively on tyrosine residues, as opposed to most other kinases that are selective for serine or threonine. The group appears to be the youngest of kinase groups, as it is absent from plants and unicellular organisms like Dictyostelium and yeast. It functions particularly in the relay of extracellular signals into the cell: over half of TKs are cell surface receptors (RTKs) and many of the others function close to the surface of the cell.

This group is very well studied, and quite diverse, and so has the largest number of distinct families of any group. Each family is classified as a receptor or cytoplasmic (or non-receptor) tyrosine kinase.

Receptor Tyrosine Kinases (RTKs)

These straddle the plasma membrane, and their kinase activity is typically activated by binding of an extracellular molecule, typically a protein growth factor. A wide variety of extracellular domains is found, but the most typical is an array of immunoglobulin (Ig) repeats, found in FGFR, PDGFR and VEGFR and other families.

FGFR

Fibroblast Growth Factor Receptors.

PVR

Vascular Endothelial and Platelet Derived Growth Factor Receptors (PDGFR/VEGFR). Major growth factor receptors with roles in angiogenesis and other tissue growth.

EGFR

Epidermal Growth Facor Receptors, found in all animals.

Tie

This pair of vertebrate-only receptors is involved in angiogenesis.

Trk

Neurotrophin receptors; important growth factor receptors that act on neuronal cells.

Eph

Ephrin receptors guide maping of optical neurons to the brain, among other functions. Invertebrates have just a single member of the family, which explodes into 14 members in vertebrates.

DDR

Discoidin Domain Receptors

CCK4

A family with a single member that is found from human all the way down to hydras. Curiously, the kinase domain is predicted to be catalytically inactive in all species, and little is known about the CCK4 function.

Sev

Includes Drosophila Sevenless (involved in eye development) and vertebrate Ros

Ryk

InsR

Receptors for insulin and insulin-like growth factor (IGF), these are important in energy homeostasis and cell growth and aging.

Ror

Ret

Alk

Anaplastic Lymphoma Kinase, involved in brain growth and in cancer

Met

TAM

Previously known as the Axl family

Musk

Lmr

RTKs that lack most or all of the extracellular region, and a long, divergent sequence beyond the cytoplasmic kinase domain (hence Lemur, after the long tail). Little is known about this family.

Kin-16 and Kin-9

These two families exist only in nematodes, where they are recently expanded. They are weakly similar to FGF receptors, and a pair of them have been weakly implicated in aging.

VKR

InsR-like kinases found in several metazoans, notably lost from Drosophila melanogaster (but not other Drosophilids) and vertebrates.

Non-receptor tyrosine kinase families

Also known as Cytoplasmic Tyrosine Kinases (CTKs) though many function in complexes tethered to the plasma membrane. Many contain SH2 and/or SH3 domains which cause them to be activated by phospo-tyrosine, often by activated receptor tyrosine kinases. SH2-containing families include all but Ack, Jak, and Fak

Src Sub-group Kinases

These four families all contain the same SH3-SH2-Kinase domain organization and all evolved prior to the emergence of animals.

Src

Abl

Tec

Csk

Other CTKs

Syk

Ack

Cytoplasmic tyrosine kinases that bind and modulate receptor signaling through interaction with small GTPases.

JAK

Janus Kinases. These are activated by receptor tyrosine kinases and in turn activate the STAT transcription factors which then translocate and activate gene expression in the nucleus.

FAK

Focal Adhesion Kinase, and its close relative Pyk2.

FER