What does the SH2 domain do?

Abstract. Src homology 2 (SH2) domains are protein modules (of approximately 100 amino acids) found in many proteins involved in tyrosine kinase signalling cascades. Their function is to bind tyrosine-phosphorylated sequences in specific protein targets.

Does IRS have SH2 domain?

These findings provide further evidence that, in response to insulin stimulation, IRS-1 acts as an SH2 docking protein that coordinates the regulation of various different signaling pathways activated by the insulin receptor.

Is SH2 a protein domain?

The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins.

What is SH2 and SH3 domains?

SH2 domains bind to short phosphotyrosine-containing sequences in growth factor receptors and other phosphoproteins. SH3 domains bind to target proteins through sequences containing proline and hydrophobic amino acids.

Where does the SH2 domain name come from?

In structural biology, SH2, or Src homology 2 domain, is a structural domain in signal transduction proteins. The Src homology 2 (SH2) domain is a protein domain of about 100 amino-acid residues first identified as a conserved sequence region between the oncoproteins Src and Fps.

What is the role for SH2 domains in signaling via receptor tyrosine kinases?

SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites.

What type of enzyme does IRS1 activate?

IRS-1 integrates signalling from insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF1R) and many other cytokine receptors and is elevated in β-catenin induced cells.

What does IRS1 protein do?

The large docking protein IRS-1 is a major substrate for the insulin receptor and other tyrosine kinases. It plays a key role in eliciting many of insulin’s actions, including binding and activation of phosphatidylinositol (PI) 3-kinase and the subsequent increase in glucose transport.

What do SH3 domains do?

The SH3 domain of Src-family PTKs, which regulate many cellular functions, such as cell proliferation and differentiation, survival, migration and cytoskeletal modifications, is mainly involved in substrate recognition and downregulation of the kinase activity.

What role do the Sh2 and SH3 domains play in the function of GRB2?

What role do Sh2 and Sh3 domains play in the function of GRB2? GRB2 is an adaptor protein. It contains one Sh2 domain, and two Sh3 domains on the N terminal and C terminal ends. Sh3 directs the binding of proline rich proteins of other compounds, and Sh2 directs the binding of tyrosine phosphorylated sequences.

What does PDZ domain stand for?

PDZ is an initialism combining the first letters of the first three proteins discovered to share the domain — post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1).

What does SH3 domain do?

Does mTOR cause insulin resistance?

A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance.

What is insulin resistance syndrome?

Collapse Section. Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body’s tissues and organs do not respond properly to the hormone insulin.

What activates IRS1?

IRS-1 integrates signalling from insulin receptor (InsR), insulin-like growth factor-1 receptor (IGF1R) and many other cytokine receptors and is elevated in β-catenin induced cells. Some evidence shows that TCF/LEF-β-catenin complexes directly regulate IRS-1.

What does SH3 domain recognize?

SH3 domains have been identified as protein modules that recognize proline-rich sequences (Mayer et al. 1988; Kaneko et al. 2008). The peptide sequence qPxqP, which binds to the SH3 domain, can be represented as two qP dipeptides linked by any residue x where q is a hydrophobic residue (Kay et al.

What is proline rich domain?

Proline-rich domains (PRDs) are ubiquitous in the eukaryotic proteome and function as docking sites for a multitude of signaling protein modules (1–4). Prolines are also favored in intrinsically disordered proteins (IDPs), which lack a well-defined structure (5, 6).

What determines the specificity of SH2 interactions with other molecules?

The target specificity of individual SH2 domains is based on the recognition of the three amino acids carboxyl terminal to the phospho-tyrosine within the target molecule.

What is the role of GRB2 protein?

The growth factor receptor-bound protein-2 (GRB2) is essential for multiple cellular functions. Inhibition of GRB2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types.

What do PDZ domains bind to?

PDZ domains bind specific sequence motifs, usually found at the very C-terminus of proteins or, more rarely, at the end of β hairpin structures. PDZ domains bind their ligands, in a manner reminiscent of PTB domains, by incorporating them through hydrogen bonds as an extra strand in a β-sheet.