The engagement of β1 integrins on promonocytic cells promotes phosphorylation of Syk and formation of a protein complex containing Lyn and β1 integrin

Abstract

The protein-tyrosine kinase Syk participates in signal transduction pathways downstream from multiple immune recognition receptors. Recent evidence indicates that Syk is also functionally coupled to cell surface integrins, which mediate interactions between the actin cytoskeleton and extracellular matrix proteins. The interactions of undifferentiated, promonocytic HL60 or U937 cells with fibronectin or anti-beta1 integrin antibodies leads to an apparent activation and tyrosine phosphorylation of Syk that is independent of tight cellular adhesion and spreading. In response to fibronectin or anti-beta1 integrin antibodies, beta1 integrins become associated with a complex of proteins that include the Lyn protein tyrosine kinase and endogenous kinase substrates of 29 and 75-80 kDa. Lyn becomes transiently activated following integrin engagement and co-localizes with the actin cytoskeleton. These studies suggest a major role for Lyn in coupling beta1 integrins to the activation of Syk.

Pharmacological comparison of LTB4‐induced NADPH oxidase activation in adherent and non‐adherent guinea‐pig eosinophils

“…In contrast to the rapid response, the syk inhibitor produced no signi®cant attenuation of the sustained phase. Although this is in agreement with the studies of CD11b/ CD18-mediated oxidase activation in human eosinophils (Lynch et al, 1999), it is a surprising result given that syk kinase has been linked with several signalling pathways that are thought to be modulated by integrins including the src family kinases, lyn and fgr (Yan et al, 1997;Miller et al, 1999), MAP kinases (Raeder et al, 1999) and PtdIns 3-kinase (Beitz et al, 1999;Craxton et al, 1999).…”

Microglial Phagocytosis of Fibrillar β-Amyloid through a β1Integrin-Dependent Mechanism

“…Immune IgG-, fA␤-, and invasin397-treated cells have similar morphologies and actin distribution, likely as the result of common signaling through Rac. Both FcR and the ␤ 1 integrin have a functional linkage to the tyrosine kinase Syk and its downstream effector Rac (Miller et al, 1999;Pradip et al, 2003). The data presented here suggest that we have uncovered a nonclassical type of phagocytosis for fA␤ that is governed by ␤ 1 integrin signaling.…”

Signal transduction involved in MCP-1–mediated monocytic transendothelial migration

“…[50][51][52][53] Syk has been reported to be activated in monocytes stimulated by the engagement of integrins. [54][55][56] Furthermore, this tyrosine kinase has been shown to control JNK activation during CD28-mediated T-cell stimulation. 35 In our model, we demonstrated that tyrosine kinases exerted a complex control on the different congeners of the MAPK family.…”