Disease relevance of AFAP1

• Genetic factors can dramatically influence the risk of colorectal cancer, and the molecular bases of many hereditary colorectal cancer syndromes, including familial adenomatous polyposis (FAP), attenuated FAP (AFAP), and hereditary nonpolyposis colorectal cancer (HNPCC) have been elucidated [1].
• Analyses of the gastrointestinal (GI) tract showed mild familial adenomatous polyposis (FAP) and numerous fundal gland polyps, indicating attenuated FAP (AFAP) [2].
• These results strongly suggest an association between sclerosing hemangioma and the AFAP [2].
• The number of polyps (50-60) seen in this patient was consistent with AFAP, as was the absence of multiple congenital hypertrophy of the retinal pigment epithelium (CHRPE) [3].
• An attenuated form of the disease (AFAP) is associated with fewer polyps, but still a high risk for colorectal cancer [4].

High impact information on AFAP1

• Taken together, these characteristics lead us to conclude that the subaxolemmal cytoskeleton in the squid giant axon is highly specialized, and is mainly composed of microtubules and a microtubule-associated HMW protein (axolinin), and actin filaments and an actin filament-associated HMW protein (255-kD protein) [5].
• We investigated the mechanism for AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in the alternatively spliced region of exon 9 [6].
• We report that the actin filament-associated protein AFAP-110 is required to mediate protein kinase Calpha (PKCalpha) activation of the nonreceptor tyrosine kinase c-Src and the subsequent formation of podosomes [7].
• Mutations at these specific binding sites on AFAP blocked mechanical stretch-induced c-Src activation [8].
• The actin filament-associated protein and Src-binding partner, AFAP-110, is an adaptor protein that links signaling molecules to actin filaments [9].

Biological context of AFAP1

• A subset of germline APC mutations results in an attenuated FAP (AFAP) phenotype, in which patients develop fewer tumors and develop them at an older age [6].
• Although a genotype-phenotype correlation between the locations of APC germline mutations and the development of AFAP has been well documented, the mechanism for AFAP has not been well defined [6].
• Accumulating evidence indicates that patients carrying germline APC mutations in the first four coding exons, in the alternatively spliced region of exon 9, or in the 3' half of the coding region usually develop AFAP [10].
• OBJECTIVES: Using a mathematical model of the human atrial action potential (AP), we aimed to: (1) evaluate the role of ionic abnormalities in producing AP changes characteristic of AF in humans and (2) explore the effects of specific channel blockade on the normal and AF-modified AP (AFAP) [11].
• Mechanical stretch increased tyrosine phosphorylation of rat AFAP and its binding to c-Src within the initial several minutes [12].

Anatomical context of AFAP1

• Calponin is an actin filament-associated regulatory protein, and its h2 isoform is expressed in lung alveolar epithelial cells under postnatal upregulation during lung development corresponding to the commencement of respiratory expansion [13].
• The differential expression of the three actin filament-associated proteins--transgelin, vimentin and MRCL3 as well as actin itself--indicates a relevant role of the actin cytoskeleton during pancreatic tumour progression [14].

Associations of AFAP1 with chemical compounds

• Here we show that mechanical stretch-induced c-Src protein tyrosine kinase activation is mediated through the actin filament-associated protein (AFAP) [8].

Other interactions of AFAP1

• The actin filament-associated protein of 110 kDa (AFAP-110) is a Src binding partner that represents a potential modulator of actin filament integrity in response to cellular signals [15].

Analytical, diagnostic and therapeutic context of AFAP1

• This case report suggests that AFAP should be included in the differential diagnosis of patients with ampullary/duodenal tumours [16].
• The activity of Src PTKs was reduced by 50% during graft reperfusion, which was associated with a decrease of Src proteins and human actin filament associated protein, a cofactor for Src activation [17].

References