"We identified 905 focal adhesion proteins, 459 of which changed in abundance with myosin II inhibition, defining the myosin-II-responsive focal adhesion proteome"

"Distributed along the actin filaments, AFAP can directly active c-Src through binding to its Src homology 3 and/or 2 domains"

"mechanical stretch-induced c-Src protein tyrosine kinase activation is mediated through the actin filament-associated protein (AFAP)"

"Knockdown of AFAP-110 expression in MDA-MB-231 cells does not result in any changes in cell proliferation but did result in a loss of actin stress fiber cross-linking and decreased adhesion to fibronectin"

"The actin filament-associated protein AFAP-110 is an actin cross-linking protein first identified as a substrate of the viral oncogene v-Src. AFAP-110 regulates actin cytoskeleton integrity but also functions as an adaptor protein that affects crosstalk between Src and PKC"

"downmodulation of AFAP-110 resulted in decreased cell-matrix adhesion and cell migration, defective focal adhesions, and reduced integrin beta1 expression"

"AFAP1 contains two PH domains (PH1 binds PKCalpha), multiple SH2- and SH3-binding motifs, a central leucine-zipper/coiled-coil that mediates multimerization, and a C-terminal actin-binding domain (ABD)"

"The protein was first identified in the early 1990s as a major substrate of the oncogenic viral tyrosine kinase v-Src and was subsequently cloned by Flynn and colleagues [PMID:8247004]"

"The leucine zipper motif serves a dual regulatory role in AFAP1 function. On one hand, it facilitates multimerization and thus enables actin crosslinking. On the other hand, it participates in an auto-inhibitory mechanism by making intramolecular contacts with sequences in the amino-terminal PH1 domain [PMID:14755689]"

"PKC phosphorylation uniquely enhances the actin crosslinking ability of AFAP1. This is in marked contrast to other actin-regulatory proteins such as fascin, MARCKS, SSeCKS, and VASP, for which PKC phosphorylation decreases actin crosslinking activity [PMID:12134071]"

"In cell lines lacking AFAP1 expression, PKC activation by phorbol esters was unable to activate c-Src or induce podosome formation. Ectopic expression of wild-type AFAP1 rescued these responses [PMID:15314167]"

"AFAP1-null mice displayed a striking lactation defect resulting in inability to efficiently nurse their pups. The lactation defect was associated with reduced c-Src activity during early lactation and selective loss of active c-Src localization at the apical surface of luminal epithelial cells [PMID:25043309]"

"Knockdown of AFAP1 expression blocked the TNF-alpha-induced reduction in P-gp efflux activity, establishing AFAP1 as essential for this regulatory mechanism at the blood-brain barrier [PMID:28112407]"

"Meta-analysis identified a common variant within the AFAP1 gene (rs4619890[G]) that conferred significantly increased risk of POAG (odds ratio = 1.20, P = 7.0 x 10^-10) [PMID:25173106]"

"In cells with elevated c-Src expression, AFAP1(403C) directs c-Src activation and podosome formation independently of upstream signals, in contrast to wild-type AFAP1 which requires PKC activation [PMID:20689769]"

"Activated forms of the Src protein-tyrosine kinase stably associate with tyrosine-phosphorylated proteins, including a protein of 110 kDa, pp110"

"AFAP-110 contains additional protein binding modules including two pleckstrin homology domains, a leucine zipper motif and a target sequence for serine/threonine phosphorylation"

"Deletion of the leucine zipper motif or PKC phosphorylation affected AFAP-110's conformation, which correlated with changes in multimerization and increased the capability of rAFAP-110 to cross-link actin filaments"

"AFAP-110 is both a substrate and binding partner of PKC. On PKC activation, stress filament organization is lost, motility structures form, and AFAP-110 colocalizes strongly with motility structures"

"An analysis of opposing binding sites indicated that the carboxy terminus/Lzip motif can contact sequences within the amino terminal pleckstrin homology (PH1) domain indicating an auto-inhibitory mechanism for regulating multimer stability and actin filament crosslinking"

"In a cell line (CaOV3) that has very little or no detectable AFAP-110, PMA treatment was unable to activate c-Src or effect podosome formation. Ectopic expression of AFAP-110 in CaOV3 cells rescued PKCalpha-mediated activation of c-Src"

"Thus PI3K activity is required for PMA-induced colocalization between AFAP-110 and cSrc and subsequent cSrc activation, and this signaling pathway promotes cell migration"

"these animals displayed a defect in lactation that resulted in an inability to nurse efficiently. Histologically, the mammary glands of the lactating knockout mice were distinguished by the accumulation of large cytoplasmic lipid droplets in the alveolar epithelial cells"

"the activity of cSrc in the mammary gland was reduced during early lactation in the AFAP1-null mouse and the localization of active cSrc at the apical surface of luminal epithelial cells during lactation was selectively lost in the absence of AFAP1"

"knockdown of AFAP-1 expression blocked the reduction in P-gp efflux activity by TNF-alpha treatment"

"We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci"

"In cells that express enhanced levels of cSrc, AFAP-110(403C) directed the activation of cSrc and the formation of podosomes independently of input signals, in contrast to wild-type AFAP-110"