title: Protein expression levels of the Src activating protein AFAP are developmentally regulated in brain.
abstract: The Src family of nonreceptor tyrosine kinases plays an important role in modulating signals that affect growth cone extension, neuronal differentiation, and brain development. Recent reports indicate that the Src SH2/SH3 binding partner AFAP-110 has the capacity to modulate actin filament integrity as a cSrc activating protein and as an actin filament bundling protein. Both AFAP-110 and a brain specific isoform called AFAP-120 (collectively referred to as AFAP) exist at high levels in chick embryo brain. We sought to identify the localization of AFAP in mouse brain in order to identify its expression pattern and potential role as a cellular modulator of Src family kinase activity and actin filament integrity in the brain. In E16 mouse embryos, AFAP expression levels were very high and concentrated in the olfactory bulb, cortex, forebrain, cerebellum, and various peripheral sensory structures. In P3 mouse pups, overall expression was reduced compared to E16 embryos, and AFAP was found primarily in olfactory bulb, cortex, and cerebellum. AFAP expression levels were significantly reduced in adult mice, with high expression levels only detected in the olfactory bulb. Western blot analysis indicated that concentrated expression of AFAP correlates well with the AFAP-120 isoform, which appears to be a splice variant of AFAP-110. As the expression pattern of AFAP overlaps with the reported expression patterns of cSrc and Fyn, we hypothesize that AFAP is positioned to modulate signal transduction cascades that direct activation of these nonreceptor tyrosine kinases and concomitant cellular changes that occur in actin filaments during brain development.
authors.affiliation: The Mary Babb Randolph Cancer Center and the Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506-9300, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Clump
authors.forename: Roger
authors.initials: R
authors.lastname: Clem
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Anne
authors.initials: A
authors.lastname: Guappone-Koay
authors.forename: Albert S
authors.initials: AS
authors.lastname: Berrebi
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Flynn
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism*; D019556:COS Cells; D030561:Databases, Nucleic Acid; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D020033:Protein Isoforms; D016415:Sequence Alignment; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C084510:AFAP 110; D033942:Adaptor Proteins, Vesicular Transport; D000906:Antibodies; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D019061:src-Family Kinases