Family

Tyrosine-protein kinase, insulin-like receptor (IPR016246)

Short name: Tyr_kinase_insulin-like_rcpt

Family relationships

Description

Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [PMID: 3291115]:

  • Serine/threonine-protein kinases
  • Tyrosine-protein kinases
  • Dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)

Protein kinase function is evolutionarily conserved from Escherichia coli to human [PMID: 12471243]. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [PMID: 12368087]. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [PMID: 15078142], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [PMID: 15320712].

Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups [PMID: 12471243]:

  • Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis [PMID: 19275641]. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction [PMID: 16700535].

  • Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [PMID: 15845350].

This entry represents the insulin receptor, as well as related insulin-like receptors. The insulin receptor binds insulin and has a tyrosine-protein kinase activity, and mediates the metabolic functions of insulin. Binding to insulin stimulates the association of the receptor with downstream mediators, including IRS1 and phosphatidylinositol 3'-kinase (PI3K). The insulin receptor can activate PI3K either directly by binding to the p85 regulatory subunit, or indirectly via IRS1. When the insulin receptor is present in a hybrid receptor with IGF1R (insulin growth factor receptor), it binds IGF1 (insulin growth factor 1) [PMID: 12138094, PMID: 16831875, PMID: 8276809].

GO terms

Biological Process

GO:0046777 protein autophosphorylation
GO:0006468 protein phosphorylation
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway

Molecular Function

GO:0005524 ATP binding
GO:0043560 insulin receptor substrate binding
GO:0043548 phosphatidylinositol 3-kinase binding
GO:0004714 transmembrane receptor protein tyrosine kinase activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PIRSF