Reactome | Recruitment of SYK to phosphorylated ITAMs

Recruitment of SYK to phosphorylated ITAMs

Stable Identifier

R-HSA-2029452

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region, cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Recruitment of SYK to phosphorylated ITAMs

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

SYK is a tyrosine kinase related to ZAP70 that is expressed in all hematopoietic cells and coimmunoprecipitates with the gamma chain associated with FCGRIIIA in macrophages and with FCERI in mast cells. SYK is very important for FCGR phagocytosis and is recruited to these phosphorylated ITAM residues through its two SRC homology 2 (SH2) domains (Agarwal et al. 1993). When SYK kinase expression is inhibited with antisense oligonucleotides both in vitro and in vivo, phagocytosis and inflammation are abolished (Matsuda et al. 1997). The domain structure of SYK comprises a regulatory region at the N-terminus consisting of a pair of SH2 domains separated by an inter-SH2 linker called interdomain A, an SH2-domain-kinase linker termed interdomain B, and a C-terminal kinase domain (Arias-Palomo et al. 2009). In resting state SYK exists in an auto-inhibited conformation by the interactions between the SH2-SH2 regulatory region and the inter-SH2 linker and the catalytic domain. This interdomain interaction reduces the conformational flexibility required by the kinase domain for catalysis (Arias-Palomo et al. 2007). Changes in the orientation of the SH2 domains could control the disruption of the auto inhibitory interactions and the activation of SYK. These movements could be totally or partially induced by the binding to phosphorylated ITAMs and/or phosphorylation of tyrosine residues in interdomain A or B (Arias-Palomo et al. 2009). Tsang et al. suggested that SYK functions as an OR-gate switch with respect to phosphorylation and ITAM binding, as either one stimulus OR the other is sufficient to cause full activation (Tsang et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
8862523	Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides Matsuda, M, Hunter, S, Wang, DC, Chien, P, Schreiber, AD, Park, JG	Mol Biol Cell	1996
7530449	Tyrosine phosphorylation and association of Syk with Fc gamma RII in monocytic THP-1 cells Fleit, HB, Bolen, JB, Ghazizadeh, S	Biochem J	1995
8340414	Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling Robbins, KC, Salem, P, Agarwal, A	J Biol Chem	1993
8226994	Cross-linking of Fc gamma receptor I (Fc gamma RI) and receptor II (Fc gamma RII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase Rankin, BM, Gilliland, LK, Schieven, GL, Bolen, JB, Kiener, PA, Burkhardt, AL, Rowley, RB, Ledbetter, JA	J Biol Chem	1993
9314552	A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages Lowell, C, Costello, PS, Turner, M, Tybulewicz, VL, DeFranco, AL, Meng, F, Crowley, MT, Fitzer-Attas, CJ	J Exp Med	1997
7522622	Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling Liu, YB, Durden, DL	Blood	1994
18818202	Molecular mechanism of the Syk activation switch Shaw, D, Papp, E, Gandhi, S, Tsang, E, Giannetti, AM, Tse, JK, Dinh, M, Wang, S, Ho, H, Bradshaw, JM	J Biol Chem	2008