Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration

Dwyer, Amy R.; Mouchemore, Kellie A.; Steer, James H.; Sunderland, Andrew; Sampaio, Natália G.; Greenland, Eloise L; Joyce, David A.; Pixley, Fiona J.

doi:10.1189/jlb.2a0815-344rr

Cited by 22 publications

(31 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 We also found that FAK activation and macrophage migration depend on SFK, as reported in other cellular contexts. 9,19,33 Moreover, FN-induced FAK activation was found to be dependent on cytoskeleton integrity, in keeping with the fact that, in response to migration stimuli, macrophages are known to polarize and extend lamellipodia and filopodia in the direction of the increasing chemotactic gradient. 34 Indeed, the formation of these protrusive structures is controlled by the dynamic reorganization of actin cytoskeleton.…”

Section: Discussionsupporting

confidence: 63%

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

Digiacomo

Tusa

Bacci

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and b1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.

show abstract

Section: Discussionsupporting

confidence: 63%

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

Digiacomo

Tusa

Bacci

et al. 2016

Cell Adhesion & Migration

View full text Add to dashboard Cite

show abstract

“…Hence, CSF-1 is considered a maturation rather than an activation factor. Consistent with this, CSF-1 stimulates differentiation of mouse and human monocytes into mature, adherent macrophages after which it remains an important survival factor [10,13,14]. CSF-1 is also a critical regulator of macrophage motility, i.e., it is a macrophage chemokine [15,16,17,18].…”

Section: Introductionmentioning

confidence: 93%

“…The system was used to demonstrate that specific CSF-1R pTyr motifs regulate macrophage morphology, while others are critical for macrophage proliferation and differentiation [44,81]. Two pTyr residues in particular were subsequently shown to regulate macrophage motility, pY721 in the kinase insert domain and pY974 at the C-terminus (Figure 3) [14,79]. …”

Section: Regulation Of Macrophage Motility By Csf-1r Signalingmentioning

confidence: 99%

“…Three of the six, Src, Fyn and Yes, are broadly expressed in most cell types, but the remaining three, Hck, Fgr and Lyn, are primarily myeloid SFKs [102]. In keeping with the role of SFKs in adhesion and motility, CSF-1-induced maturation of macrophages from non-adherent precursor cells into adherent, migratory macrophages, produces marked changes in the expression of Src, Fyn and Fgr [14]. While there are specific biological effects for each of the SFKs expressed in macrophages, overlapping effects are common [103].…”

Section: Csf-1r Py974 Sfks and Macrophage Motilitymentioning

confidence: 99%

“…Indeed, the expression levels of individual SFKs may be coupled with those of other SFKs. For example, a striking reduction in Src levels is associated with increased Hck and Fgr expression in macrophages expressing a CSF-1R with a mutation in the C-terminal tyrosine (Y974F) and these macrophages have reduced motility (Figure 3) [14]. Accordingly, pan-SFK targeting inhibits CSF-1-stimulated motility and invasion in macrophages [14].…”

Section: Csf-1r Py974 Sfks and Macrophage Motilitymentioning

confidence: 99%

See 2 more Smart Citations

Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling

Dwyer

Greenland

Pixley

2017

Cancers

View full text Add to dashboard Cite

Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage’s interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1). CSF-1 also regulates macrophage survival, proliferation and differentiation, and its many effects are transduced by its receptor, the CSF-1R, via phosphotyrosine motif-activated signals. Mutational analysis of CSF-1R signaling indicates that the major mediators of CSF-1-induced motility are phosphatidyl-inositol-3 kinase (PI3K) and one or more Src family kinase (SFK), which activate signals to adhesion, actin polymerization, polarization and, ultimately, migration and invasion in macrophages. The macrophage transcriptome, including that of the motility machinery, is very complex and highly responsive to the environment, with selective expression of proteins and splice variants rarely found in other cell types. Thus, their unique motility machinery can be specifically targeted to block macrophage migration, and thereby, inhibit tumor invasion and metastasis.

show abstract

Bionanoparticle‐Based Delivery in Antihypertensive Vaccine Mediates DC Activation through Lipid‐Raft Reorganization

Xiao

Shi

et al. 2020

Adv Funct Materials

View full text Add to dashboard Cite

Bionanoparticles (BNPs) are widely used as vaccine carriers. Compared with classic protein carriers, BNPs exhibit nanostructures that enable them to interaction with biointerface-like cell membrane or membrane domains. An antihypertensive vaccine ATR-NP is produced based on a virus-like particle (VLP) Qβ carrier. Qβ shows great delivery efficiency and immunogenicity to antigen-presenting cells (APCs) such as dendritic cells (DCs), and DC activation induced by ATR-NP is highly dependent on membrane lipid rafts. Further studies reveal that ATR-NP exhibits tight affinity to rafts, and interface effects between them prompt membrane phase separation and raft accumulation through NP-induced membrane curvature change. Lipid rafts are accumulated and expanded together with a decline of their diffusion in membrane,which benefits signaling protein Src partition in rafts. The heterogeneous protein partition implies functional centralization for stronger signal transduction. In conclusion, targeting and reorganizing membrane domains such as lipid rafts suggests BNPs could be used as vaccine carriers and is a potent strategy for vaccine and other immunological agent design.

show abstract

Src family kinase expression and subcellular localization in macrophages: implications for their role in CSF-1-induced macrophage migration

Cited by 22 publications

References 65 publications

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway

Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling

Bionanoparticle‐Based Delivery in Antihypertensive Vaccine Mediates DC Activation through Lipid‐Raft Reorganization

Contact Info

Product

Resources

About