Reactome | Phosphorylation of beta and gamma subunits by LYN

Phosphorylation of beta and gamma subunits by LYN

Stable Identifier

R-HSA-2454208

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Phosphorylation of beta and gamma subunits by LYN

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Upon FCGRI-IgE aggregation, LYN kinase phosphorylates the tyrosine residues within the ITAM (immunoreceptor tyrosine-based activation motifs) of both the beta and gamma subunits. The detailed mechanism of the initial engagement of LYN kinase and FCERI is incompletely understood, but two different models have been proposed. One model postulates that a small fraction of LYN is constitutively bound to beta subunit of FCERI prior to activation. Aggregation of FCERI facilitates the transphosphorylation of one FCERI by LYN bound to a juxtaposed receptor (Vonakis et al. 1997, Draber & Draberova 2002). Alternative model postulates that LYN is observed in lipid rafts enriched in glycosphingolipids, cholesterol, and glycosylphosphatidylinositol-anchored proteins and upon aggregation, FCERI rapidly translocates into lipid rafts, where it is phosphorylated by LYN kinase. Either the association of LYN or FCERI or both with lipid rafts is important for initiating this phosphorylation process (Young et al. 2003, Kovarova et al. 2002, Draber & Draberova 2002).
Beta subunit ITAM differs from canonical ITAMs in two ways; the spacing between the two canonical tyrosines harbours a third tyrosine, and it is one amino acid shorter than in canonical ITAMs, thus making it unfit to bind and recruit Syk. Among the three tyrosine residues (Y219, Y225 and Y229), Y219 may play a predominant role in beta chain function and LYN recruitment. Mutation of this tyrosine would decrease substantially LYN association and subsequent phosphorylation of Y225 and Y229. This would result in decreased gamma phosphorylation and decreased SYK recruitment and activation (On et al. 2004).

Literature References

PubMed ID	Title	Journal	Year
12217391	Lipid rafts in mast cell signaling Dráber, P, Dráberová, L	Mol. Immunol.	2002
11713268	Structure-function analysis of Lyn kinase association with lipid rafts and initiation of early signaling events after Fcepsilon receptor I aggregation Kovárová, M, Rivera, J, Tolar, P, Dráber, P, Arudchandran, R, Dráberová, L	Mol. Cell. Biol.	2001
7526393	Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation Pribluda, C, Metzger, H, Pribluda, VS	Proc. Natl. Acad. Sci. U.S.A.	1994
12670955	A lipid raft environment enhances Lyn kinase activity by protecting the active site tyrosine from dephosphorylation Baird, B, Young, RM, Holowka, D	J. Biol. Chem.	2003
9295361	The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE Vonakis, BM, Metzger, H, Haleem-Smith, H, Chen, H	J. Biol. Chem.	1997