Search results for IRS1

Showing 13 results out of 66

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Types

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Complex (6 results from a total of 14)

Identifier: R-HSA-9712076
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-5686316
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-198344
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-213135
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9603435
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-2445094
Species: Homo sapiens
Compartment: plasma membrane

Reaction (6 results from a total of 34)

Identifier: R-HSA-9700156
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Phosphorylated tyrosine 1096 is the docking site for IRS1 on the active full length- ALK receptor. IRS-mediated signaling simulates the MAP kinase and PI3K pathways and contributes to cellular proliferation in a manner that depends on ALK kinase activity (Motegi et al, 2004; Kuo et al, 2007; reviewed in Turner and Alexander, 2006; Roskoski, 2013; Della Corte et al, 2018).
Identifier: R-HSA-74747
Species: Homo sapiens
Compartment: cytosol
At the beginning of this reaction, 1 molecule of 'phospho-IRS' is present. At the end of this reaction, 1 molecule of 'Orthophosphate', and 1 molecule of 'IRS' are present.

This reaction takes place in the 'cytosol' and is mediated by the 'protein tyrosine phosphatase activity' of 'protein tyrosine phosphatase' (Pederson et al.2001).
Identifier: R-HSA-74737
Species: Homo sapiens
Compartment: cytosol
IRS1, IRS2 and IRS3 are all known to bind the regulatory subunit of PI3K via its SH2 domain, an interaction that itself activates the kinase activity of the PI3K catalytic subunit (Rivachandran et al. 2001).
Identifier: R-HSA-198211
Species: Homo sapiens
Compartment: cytoplasmic side of plasma membrane
IRS1 and IRS2 bind directly to TRK receptors phosphorylated at Y490, through their phosphotyrosine- binding (PTB) domains.
Identifier: R-HSA-2671873
Species: Homo sapiens
Compartment: plasma membrane, cytosol
SH2B1 in the LEP:LEPR:JAK2:SH2B1 complex can bind either IRS1 or IRS2 (Duan et al. 2004, Li et al. 2007). The binding brings IRS1/2 into proximity with JAK2 for phosphorylation.
Identifier: R-HSA-74736
Species: Homo sapiens
Compartment: cytosol
Inactive p21ras:GDP is anchored to the plasma membrane by a farnesyl residue. Insulin stimulation results in phosphorylation of IRS1/2 on tyrosine residues. GRB2 binds the phosphotyrosines via its SH2 domain. As IRS is phosphorylated by the insulin receptor near to the plasma membrane, the GRB2:SOS1:IRS interaction brings SOS1 and p21 Ras into close proximity.

Pathway (1 results from a total of 7)

Identifier: R-HSA-201556
Species: Homo sapiens
The anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase that, along with related receptor LTK (leukocyte tyrosine kinase receptor) is a member of the insulin receptor superfamily (Iwahara et al, 1997). ALK was discovered as an oncogene in anaplastic large cell lymphomas (ALCLs), but also plays an oncogenic role in other cancer types, such as non-small-cell lung cancer (NSCLC), inflammatory myofibroblastic tumours (IMT), melanoma, neuroblastoma and glioblastoma. In cancer, the chromosomal region encoding ALK frequently undergoes genomic rearrangements, resulting in the formation of ALK fusion proteins, such as NPM‑ALK (the result of a translocation event, t(2;5)(p23;q35) which is predominant in ALCL) and EML4‑ALK (an inversion event on chromosome 2) (Morris et al, 1994; Couts et al, 2018). These fusion proteins consist of the C‑terminal region of ALK, encompassing the kinase domain and the effector protein binding domain (with loss of the transmembrane domain), while the N‑terminus of the fusion protein contains the dimerization domain of the partner gene. Fusion proteins of ALK are therefore capable of ligand‑independent dimerization, resulting in constitutive ALK signaling (reviewed in Duyster et al, 2001; Chiarle et al, 2008; Della Corte et al, 2018; Hallberg and Palmer, 2013; Hallberg and Palmer, 2016; Janoueix-Larousey et al, 2018; Ducray et al, 2019). Additionally, amplification of ALK and/or point mutations leading to its constitutive activation have been detected in neuroblastoma (reviewed in McDuff et al, 2011).

Many of the functional studies on ALK have been conducted in the context of oncogenic forms of the protein. In contrast, fewer studies have been conducted on the wild type protein under normal physiological conditions, and indeed, ALK was initially classed as an orphan receptor with no identified ligand. Two small heparin-binding growth factors, pleiotrophin (PTN) and midkine (MDK), were initially identified as potential ligands however subsequent studies failed to support this (Stoica et al, 2001; Stoica et al, 2002; Mathivet et al, 2007; Moog-Lutz et al, 2005; Motegi et al, 2004; reviewed in Wellstein et al, 2012; Winkler et al, 2014; Herradon and Perez-Garcia, 2014). More recently, ALKAL1 and ALKAL2 (also known as FAM150A and FAM150B) have been identified as ligands for both ALK and the related LTK receptor, albeit with differing potencies (Zhang et al, 2014; Guan et al, 2015; Reshetnyak et al, 2015; Reshetnyak et al, 2018; Fadeev et al, 2018; Reshetnyak et al, 2021; De Munck et al, 2021; Borenas et al, 2021; reviewed in Hallberg and Palmer, 2016). Whereas LTK receptor is potently activated by both ALKAL1 and ALKAL2, ALK is only weakly stimulated by ALKAL1 (Reshetnyak et al, 2015; Reshetnyak et al, 2018). Ligand binding induces the dimerization of the receptor and transautophosphorylation, resulting in a fully activated receptor that triggers downstream signaling cascades such as RAS, PI3K and IRS1 signaling. ALK may also undergo ligand-independent activation through RPTPB/RPTPZ (Deuel et al, 2013).

ALK is mainly expressed in the developing central and peripheral nervous system and plays a role in differentiation during development (Souttou et al, 2001; Gouzi et al, 2005; Degoutin et al, 2007). In Drosophila and mice, ALK is a thinness gene involved in the resistance to weight gain (Orthofer et al, 2020). Through activation of STAT3 targets, ALK also appears to play a role in response to ethanol (Hamada et al, 2021).
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