Human Interaction Network Ontology

Last uploaded: June 27, 2014
Preferred Name

JAK2 phosphorylation
Synonyms
Definitions

has a Stoichiometric coefficient of 4 Authored: Jupe, S, 2010-10-14 Reviewed: Waters, MJ, 2011-06-23 Edited: Jupe, S, 2011-06-10 Similar models explain JAK activation by the cytokine-like hormone receptors (GHR and PRLR) and interleukin receptors. JAK2 activation is believed to occur as mutual transactivation whereby JAK2 bound to one receptor chain phosphorylates JAK2 bound to the other receptor chain in the dimeric receptor. Transactivation is widely accepted (Herrington & Carter-Su 2001) having been originally proposed in the 1990's (Quelle et al. 1994, Hou et al. 2002). JAK phosphorylation is thought to lock the kinase domain in an active state; prior to this JAK2 is held in an inactive state by interactions between its kinase and pseudokinase domains (Giordanetto & Kroemer 2002). Although there are structures of JAK kinase domains (e.g. Lucet et al. 2006), no complete JAK structures are available and the activation mechanism remains poorly understood (Brooks & Waters 2010). The trigger for JAK activation is believed to be a conformational change in the receptor when ligand is bound, leading to a rotation of the cytoplasmic regions which brings the catalytic domains of bound JAK2 molecules into close proximity and frees them from inhibition by the pseudokinase domains. Supporting observations for cytokine-like hormone receptors include: JAK2 becomes tyrosine phosphorylated as a consequence of GHR activation by GH (Argetsinger et al. 1993); JAK2 is activated following PRLR activation (Campbell et al. 1994, Rui et al. 1994); forced dimerization of GH receptor domains is sufficient to activate signaling (Behncken et al. 2000); phosphorylation of JAK2 at Y1007 is critical for kinase activation (Feng et al. 1997, Lucet et al. 2006); JAK autophosphorylation at several other sites appears to regulate activity (e.g. Feener et al. 2004, Argetsinger et al. 2004, 2010). Only the Y1007 phosphorylation is represented in this reaction. Reviewed: Herington, AC, 2011-06-13

ID

http://purl.obolibrary.org/obo/HINO_0024409

comment

has a Stoichiometric coefficient of 4

Authored: Jupe, S, 2010-10-14

Reviewed: Waters, MJ, 2011-06-23

Edited: Jupe, S, 2011-06-10

Similar models explain JAK activation by the cytokine-like hormone receptors (GHR and PRLR) and interleukin receptors. JAK2 activation is believed to occur as mutual transactivation whereby JAK2 bound to one receptor chain phosphorylates JAK2 bound to the other receptor chain in the dimeric receptor. Transactivation is widely accepted (Herrington & Carter-Su 2001) having been originally proposed in the 1990's (Quelle et al. 1994, Hou et al. 2002). JAK phosphorylation is thought to lock the kinase domain in an active state; prior to this JAK2 is held in an inactive state by interactions between its kinase and pseudokinase domains (Giordanetto & Kroemer 2002). Although there are structures of JAK kinase domains (e.g. Lucet et al. 2006), no complete JAK structures are available and the activation mechanism remains poorly understood (Brooks & Waters 2010). The trigger for JAK activation is believed to be a conformational change in the receptor when ligand is bound, leading to a rotation of the cytoplasmic regions which brings the catalytic domains of bound JAK2 molecules into close proximity and frees them from inhibition by the pseudokinase domains. Supporting observations for cytokine-like hormone receptors include: JAK2 becomes tyrosine phosphorylated as a consequence of GHR activation by GH (Argetsinger et al. 1993); JAK2 is activated following PRLR activation (Campbell et al. 1994, Rui et al. 1994); forced dimerization of GH receptor domains is sufficient to activate signaling (Behncken et al. 2000); phosphorylation of JAK2 at Y1007 is critical for kinase activation (Feng et al. 1997, Lucet et al. 2006); JAK autophosphorylation at several other sites appears to regulate activity (e.g. Feener et al. 2004, Argetsinger et al. 2004, 2010). Only the Y1007 phosphorylation is represented in this reaction.

Reviewed: Herington, AC, 2011-06-13

definition source

Pubmed16174768

Pubmed11445442

Pubmed20664532

Pubmed10828073

Pubmed8188682

Reactome, http://www.reactome.org

Pubmed12456871

Pubmed15143188

Pubmed8343952

Pubmed7515493

Pubmed12479803

Pubmed9111318

Pubmed20304997

Pubmed7508935

Pubmed8007942

has input

http://purl.obolibrary.org/obo/HINO_0021883

http://purl.obolibrary.org/obo/CHEBI_15422

has output

http://purl.obolibrary.org/obo/CHEBI_16761

http://purl.obolibrary.org/obo/HINO_0021878

label

JAK2 phosphorylation

prefixIRI

HINO:0024409

prefLabel

JAK2 phosphorylation

seeAlso

Reactome Database ID Release 43982810

ReactomeREACT_111076

subClassOf

http://purl.obolibrary.org/obo/INO_0000040

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