RGD Reference Report - Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. - Rat Genome Database

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Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors.

Authors: Finnemann, SC 
Citation: Finnemann SC EMBO J 2003 Aug 15;22(16):4143-54.
RGD ID: 1299194
Pubmed: PMID:12912913   (View Abstract at PubMed)
PMCID: PMC175805   (View Article at PubMed Central)
DOI: DOI:10.1093/emboj/cdg416   (Journal Full-text)

Daily alphavbeta5 integrin-dependent phagocytosis of spent photoreceptor outer segment fragments by the retinal pigment epithelium (RPE) is critical for retinal function. This study identifies a key role for focal adhesion kinase (FAK) in RPE phagocytosis. Particle binding increases FAK complex formation with alphavbeta5 receptors at the apical, phagocytic RPE surface and activates FAK. Subsequent particle engulfment coincides with dissociation of activated FAK from alphavbeta5. Mutant FAK retaining focal adhesion targeting but lacking kinase activity interferes with recruitment of full-length FAK to alphavbeta5 and abrogates FAK activation in response to RPE phagocytic challenge. Such inhibition of FAK signaling has no effect on alphavbeta5-dependent binding of particles but blocks their engulfment. Conversely, FAK re-expression promotes particle engulfment by FAK null fibroblasts. Selective ligation of alphavbeta5 receptors at the apical RPE surface is sufficient to phosphorylate and mobilize FAK. Furthermore, FAK phagocytic signaling is independent of the internalization receptor MerTK. In contrast, inhibition of FAK signaling diminishes MerTK phosphorylation. These results demonstrate that FAK provides an essential link between binding and engulfment mechanisms of integrin-mediated phagocytosis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of phagocytosis  IMP 1299194 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane  IDA 1299194 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein-containing complex binding  IPIItgb5 (Rattus norvegicus) and Itgav (Rattus norvegicus)1299194 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptk2  (protein tyrosine kinase 2)

Objects referenced in this article
Gene Itgb5 integrin subunit beta 5 Rattus norvegicus
Gene Mertk MER proto-oncogene, tyrosine kinase Rattus norvegicus

Additional Information