Sequestering and phosphorylation Fc gamma receptors in the lipid rafts

Stable Identifier
Reaction [omitted]
Homo sapiens
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After cross linking, Fc gamma receptors are sequestered to lipid rafts where they are complexed with some of the tyrosine kinases of Src family and undergo phosphorylation on the tyrosine residues contained in conserved ITAM sequences. At least six out of nine members of the Src family kinases (SRC, FYN, FGR, HCK, YES and LYN ) have been identified in the phagocytic cells and are implicated in the initiation of Fc gamma mediated signaling. (Suzuki et al. 2000, Majeed et al. 2001, Kwiatkowska et al. 2003). Some of these kinases have been found associated with specific receptors. In monocytes HCK and LYN have been found associated with FCGRI (Durden et al. 1995), whereas only HCK with FCGRIIA (Ghazizadeh et al. 1994) while FGR in neutrophils (Hamada et al. 1993) and LCK in NK cells with FCGRIIIA (Pignata et al. 1993)
The implication of Src kinases in phosphorylation was first supported by pharmacological findings that herbimycin A, a tyrosine kinase inhibitor relatively specific for Src-family kinases, potently suppressed Fc receptor mediated functions (Greenberg et al. 1993, Suzuki et al. 2000). However, their particular involvement in phagocytosis remains unclear, as targeted disruption of single or multiple Src family genes did not result in significant alterations in phagocytosis (Hunter et al. 1993, Fitzer Attas et al. 2000, Suzuki et al. 2000). HCK, FGR and LYN triple-deficient (-/-) macrophages have shown significant delays in FCGR mediated phagocytosis, but these deficiencies do not completly disrupt the process (Fitzer Attas et al. 2000).
Tyrosine residues Y288 and Y304 (Y282 and Y298 according to the literature reference, it is 6 residues shorter compared to uniprot entry due to an alternate initiation codon usage), within ITAM sequence in the cytoplasmic domain of FCGRIIA are the key target sites that are phosphorylated by Src family kinases (Mitchell et al, 1994). In case of FCGRIA and FCGRIIIA the specific tyrosine residues within ITAMs of the associated gamma/zeta chains are phosphorylated by activated Src family kinases (SFKs) (Park et al. 1993).
Literature References
PubMed ID Title Journal Year
10861086 Differential involvement of Src family kinases in Fc gamma receptor-mediated phagocytosis

Okada, M, Honda, Z, Hirose, N, Yamamoto, T, Suzuki, T, Kono, H, Yamamoto, K

J Immunol 2000
1372004 Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII

Huang, MM, Brugge, JS, Hoxie, JA, Indik, Z, Brass, LF, Schreiber, AD

J Biol Chem 1992
16921024 Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis

Indik, ZK, Worth, RG, Kim, MK, Barreda, DR, Huang, ZY, Chien, P, Schreiber, AD

J Leukoc Biol 2006
9000504 Tyrosine phosphorylation and Fcgamma receptor-mediated phagocytosis

Strzelecka, A, Kwiatkowska, K, Sobota, A

FEBS Lett 1997
Catalyst Activity

protein tyrosine kinase activity of Src family kinases (SFKs) [cytosol]

Orthologous Events
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