Search results for JAK1

Showing 26 results out of 335

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Protein (5 results from a total of 6)

Identifier: R-HSA-451898
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: P23458
Identifier: R-HSA-8983168
Species: Homo sapiens
Compartment: endosome
Primary external reference: UniProt: P23458
Identifier: R-HSA-451921
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: JAK1: P23458
Identifier: R-HSA-8950711
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: JAK1: P23458
The receptor chains are also utilized by multiple cytokines (Fig. 1)1,2. IL-12 signals via IL12Rβ1 and IL12Rβ248,71,72, while IL-23 signals through IL12Rβ1 and IL23R69,73. In contrast, IL-27 utilizes gp130 and WSX-174, while IL-35 signals via gp130 and IL12Rβ228. IL-35 is unusual in that it can also signals via two additional receptor chain compositions; gp130-gp130 and IL12Rβ2-lL12Rβ2 homodimers28.
Signaling via all of these receptors is mediated by members of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) family27,75,76 (Fig. 1). JAK2 and either JAK1 or TYK2 appear to mediate phosphorylation of the IL-12 cytokine receptors family-associated STATs. IL-12 mediates signaling via pSTAT477, IL-23 via pSTAT3 and pSTAT469,73, IL-27 via pSTAT1 and pSTAT378,79, and IL-35 via pSTAT1 and pSTAT428. For IL-35, formation of a STAT1:STAT4 heterodimer is required for Ebi2/ Il12a transcription, but partially dispensable for supression28 (PMID:22814351)
Identifier: R-HSA-1112543
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: JAK1: P23458

Reaction (5 results from a total of 147)

Identifier: R-HSA-873918
Species: Homo sapiens
Compartment: cytosol, plasma membrane
The initial phosphorylation of JAK1 and JAK2 is mediated by JAK2. Autophosphorylated JAK2 may transphopshorylate JAK1 bound to IFNGR1 chain. Tyrosine 1033 in the activation loop of the JAK1 kinase domain may be the target for transphosphorylation (phosphorylation site mentioned here is based on sequence similarity with all the other JAK kinases).
Identifier: R-HSA-8987012
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
Tyrosine-protein kinase JAK1 (JAK1) is phosphorylated after Interleukin-24 (IL24) ligand interaction with its receptor. There are two IL24 receptors. One consists of Interleukin-20 receptor subunit alpha (IL20RA), Tyrosine-protein kinase JAK1 (JAK1) and Interleukin-20 receptor subunit beta (IL20RB), the other, represented in this event, uses interleukin-22 receptor subunit alpha-1 (IL22RA1) instead of IL20RA (Dumoutier et al. 2001, Wang et al. 2002). IL22RA1 can bind JAK1 (Ferrao et al. 2016). IL24 can stimulate JAK1 phosphorylation in human colonic subepithelial myofibroblasts, where the components of both forms of the IL24 receptor are expressed (Andoh et al. 2009). It has been demonstrated that both forms of the IL24 receptor can activate STAT3 (Dumoutier et al. 2001, Wang et al. 2002). Based on the consensus understanding of JAK/STAT signaling, STAT3 activation is very likely to be preceded by JAK1 phosphorylation and it is therefore likely that JAK1 is phosphorylated in both forms of the IL24 receptor. This is a black box event because it has not been established that both forms of the IL24 receptor are involved in JAK1 phosphorylation.
Identifier: R-HSA-8987043
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Tyrosine protein kinase JAK1 (JAK1) binds to Interleukin-22 receptor subunit alpha 1 (IL22RA1). IL22RA1 was identified as one of several interleukin receptors able to bind JAK1 in coimmunoprecipitation experiments (Ferrao et al. 2016).
Identifier: R-HSA-451900
Species: Homo sapiens
Compartment: cytosol, plasma membrane
Janus Kinase 1 (JAK1) constitutively associates with IL-2R beta.
Identifier: R-HSA-8987120
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
Tyrosine protein kinase JAK1 (JAK1) binds Interferon lambda receptor 1 (IFNLR1).
The Box1 of IFNLR1 binds to the F2 subdomain of the JAK1 FERM, in a cleft formed by helices F2 alpha2, F2 alpha3, and F2 alpha4 (Ferrao et al. 2017).

Complex (5 results from a total of 162)

Identifier: R-HSA-8987233
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-9674578
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-451918
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-451943
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-873803
Species: Homo sapiens
Compartment: plasma membrane

Set (5 results from a total of 6)

Identifier: R-HSA-9674547
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-1112596
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-1067656
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8950211
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-8985446
Species: Homo sapiens
Compartment: cytosol

Pathway (5 results from a total of 13)

Identifier: R-HSA-9674555
Species: Homo sapiens
CSF3 (GCSF) is a cytokine that regulates production of neutrophils and granulocytes (reviewed in Panopoulos and Watowich 2008). CSF3 circulates extracellularly as a dimer and binds to the monomeric receptor CSF3R (GCSFR) on neutrophil precursors and mature neutrophils (reviewed in Futosi et al. 2013). CSF3R possesses no catalytic activity of its own and is constitutively associated with the kinases LYN (Corey et al. 1994) and JAK1 (Nicholson et al. 1994). Upon binding the CSF3 dimer, CSF3R dimerizes, is phosphorylated, and activates JAK-STAT signaling, RAS-RAF-MEK-ERK signaling, and PI3K signaling (reviewed in Basu et al. 2002, Roberts et al. 2005, Kendricks and Bogoyevitch 2007, Touw and van de Geijn 2007).
After dimerization of CSF3R, JAK1 associated with CSF3R is required for phosphorylation of tyrosine residues in the cytosolic domain of CSF3R which recruit further kinases such as JAK2, SYK, HCK, and TYK2 (reviewed in Sampson et al. 2007). Phosphorylated JAK1 and JAK2 then appear to act redundantly to phosphorylate STAT proteins (STAT1, STAT3, STAT5) which dimerize and transit to the nucleus to activate gene expression.
CSF3 signaling also activates the RAS pathway, resulting in activation of ERK1 and ERK2 and cellular proliferation. Phosphorylated CSF3R recruits both GRB2, which can act as a scaffold for RAS guanyl exchange factors SOS and VAV, and PTPN11 (SHP2), which activates RAS by dephosphorylating tyrosine-32 of RAS (Bunda et al. 2015). Association of SOS or VAV with the phosphorylated CSF3R has not yet been shown. The pathway to activation of PI3K is uncertain but appears to proceed via GAB2 bound to CSF3R.
Mutations in CSF3R can occur during the course of Kostmann disease, a severe congenital neutropenia (reviewed in Zeidler and Welte 2002, Zeidler 2005, Ward 2007, Vandenberghe and Beel 2011). Somatic mutations in CSF3R, principally truncations of the C-terminal region, are involved in the pathogenesis of severe congenital neutropenia and are associated with progression to acute myeloid leukemia (Dong et al. 1995, reviewed in Ward 2007, Beekman and Touw 2010, Xing and Zhao 2016). Loss or mutation of the C-terminal region of CSF3R interferes with inhibition and turnover of the receptor. Mutation of Thr-618 to Ile-618 in CSF3R causes spontaneous dimerization and consequent autoactivation leading to CSF3-independent signaling and chronic neutrophilic leukemia (Maxson et al. 2013).
Identifier: R-HSA-8985947
Species: Homo sapiens
Interleukin 9 (IL9) binds interleukin 9 receptor a chain (IL9R) and the interleukin 2 receptor common gamma chain (IL2RG) to initiate IL9 signaling downstream cascade. IL9R colocalize with Interleukin 2 receptor α chain and MHC molecules in lipid rafts of human T lymphoma cells (Nizsalóczki et al. 2014). IL2RG is essential for IL9 dependent growth signal transduction (Kimura et al. 1995). IL9R (glycoprotein of 64 kDa) has saturable and specific binding sites with a Kd of 100 pM (Renauld et al. 1992). The activated IL9R complex recruits tyrosine kinase proteins from the Janus kinase (JAK) family: JAK1 (JAK1) and JAK3 (JAK3) for subsequent activation of the Signal transducer and activator of transcription (STAT) factors STAT1, STAT3 and STAT5. The activated STATs form STAT5 dimers and STAT1:STAT3 heterodimers (Neurath & Finotto 2016, Li & Rostami 2010).
Identifier: R-HSA-9020958
Species: Homo sapiens
Interleukin-21 (IL21) is a pleiotropic cytokine with four alpha-helical bundles. It is produced primarily by natural killer T cells, T follicular helper cells and TH17 cells, with lower levels of production by numerous other populations of lymphohaematopoietic cells (Spolski & Leonard 2014). IL21 binds Interleukin-21 receptor (IL21R, NILR) and Cytokine receptor common subunit gamma (IL2RG, GammaC).
IL21R has significant homology with the class I cytokine receptors Interleukin-2 receptor subunit beta (IL2RB) and Interleukin-4 receptor subunit alpha (IL4R) and was predicted to similarly form a complex with IL2RG. IL21R dimers can weakly bind and signal in response to IL21 but IL21 generates a much stronger response when IL21R is combined with IL2RG, which is required for a fully signaling capable IL21 receptor complex (Ozaki et al. 2000, Asao et al. 2001, Habib et al. 2002). IL21R can bind Janus kinase 1 (JAK1) (Ozaki et al. 2000) but IL2RG is required for IL21 induced signaling (Asao et al. 2001). The heteromeric IL21 receptor complex can activate JAK1, JAK3, Signal transducer and activator of transcription 1 (STAT1), STAT3, STAT4 and STAT5, depending on the cell type. In cultured T-cells IL21 induced phosphorylation of JAK1, JAK3, STAT1, STAT3 and weakly STAT5 (Asao et al. 2001). In primary CD4+ T cells IL21 induced the phosphorylation of STAT1 and STAT3 but not STAT5, whereas IL2 induced the phosphorylation of STAT5 and STAT1 but not STA3 (Bennet et al. 2003). IL21 stimulation of primary splenic B cells and the pro-B-cell line Ba-F3 induced the activation of JAK1, JAK3 and STAT5 (Habib et al. 2002). In primary human NK cells or the NK cell line NK-92, IL21 induced the activation of STAT1, STAT3, and STAT4 but not STAT5 (Strengell et al. 2002, 2003). IL21 activated STAT1 and STAT3 in human monocyte-derived macrophages (Vallières & Girard 2017).
Identifier: R-HSA-451927
Species: Homo sapiens
Compartment: plasma membrane
The interleukin-2 family (also called the common gamma chain cytokine family) consists of interleukin (IL)2, IL9, IL15 and IL21. Although sometimes considered to be within this family, the IL4 and IL7 receptors can form complexes with other receptor chains and are represented separately in Reactome. Receptors of this family associate with JAK1 and JAK3, primarily activating STAT5, although certain family members can also activate STAT1, STAT3 or STAT6.
Identifier: R-HSA-8983432
Species: Homo sapiens
The high affinity Interleukin-15 receptor is a heterotrimer of Interleukin-15 receptor subunit alpha (IL15RA), Interleukin-2 receptor subunit beta (IL2RB, CD122) and Cytokine receptor common subunit gamma (IL2RG, CD132). IL2RB and IL2RG are also components of the Interleukin-2 (IL2) receptor. Treatment of human T cells with Interleukin-15 (IL15) results in tyrosine phosphorylation of Tyrosine-protein kinase JAK1 (JAK1, Janus kinase 1) and Tyrosine-protein kinase JAK3 (JAK3, Janus kinase 3) (Johnston et al. 1995, Winthrop 2017). IL15 can signal by a process termed 'trans presentation', where IL15 bound by IL15 on one cell is trans-presented to IL2RB:IL2RG on another cell (Dubois et al. 2002) but can also participate in more 'traditional' cis signaling (Wu et al. 2008, Mishra et al. 2014) where all the three receptors are present on the same cell. Stimulation of lymphocytes by IL15 release MAPK activation through GAB2/SHP2/SHC (GRB2-associated-binding protein 2/Tyrosine-protein phosphatase non-receptor type 11/SHC transforming protein 1 or 2) cascade activation (Gadina et al. 2000).

Icon (1 results from a total of 1)

Species: Homo sapiens
Curator: Steve Jupe
Designer: Cristoffer Sevilla
JAK1 icon
Tyrosine-protein kinase JAK1
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