Spectrin is a widely expressed protein with specific isoforms found in erythroid and nonerythroid cells. Spectrin contains an Src homology 3 (SH3) domain of unknown function. A cDNA encoding a candidate spectrin SH3 domain-binding protein was identified by interaction screening of a human brain expression library using the human erythroid spectrin (alpha I) SH3 domain as a bait. Five isoforms of the alpha I SH3 domain-binding protein mRNA were identified in human brain, Mapping of SH3 binding regions revealed the presence of two alpha I SH3 domain binding regions and one Abl-SH3 domain binding region. The gene encoding the candidate spectrin SH3 domain-binding protein has been located to human chromosome 10p11.2 --> p12. The gene belongs to a recently identified family of tyrosine kinase-binding proteins, and one of its isoforms is identical to e3B1, an eps8-binding protein (Biesova, Z., Piccoli, C., and Wong, W. T. (1997)Oncogene 14, 233-241). Overexpression of the green fluorescent protein fusion of the SH3 domain-binding protein in NIH3T3 cells resulted in cytoplasmic punctate fluorescence characteristic of the reticulovesicular system. This fluorescence pattern was similar to that obtained with the anti-human erythroid spectrin alpha I Sigma I/beta I Sigma I antibody in untransfected NIH3T3 cells; in addition, the anti-alpha I Sigma I/beta I Sigma I antibody also stained Golgi apparatus. Immunofluorescence obtained using antibodies against alpha I Sigma I/beta I Sigma I spectrin and Abl tyrosine kinase but not against alpha II/beta II spectrin colocalized with the overexpressed green fluorescent protein-SH3-binding protein. Based on the conservation of the spectrin SH3 binding site within members of this protein family and published interactions, a general mechanism of interactions of tyrosine kinases with the spectrin-based membrane skeleton is proposed.

Amyloid β protein 1–40 (Aβ40) and Aβ42 levels were quantitated in plasma from 43 persons with Down syndrome (DS; 26–68 years of age), 43 age-matched normal controls, and 19 non-DS mentally retarded (MR) persons (26–91 years of age) by using a sandwich enzyme linked immunosorbent assay. Aβ40 levels were higher in DS and MR than controls, but were similar between DS and MR groups. Aβ42 levels were higher in DS than controls or MR persons. The ratios of Aβ42/Aβ40 were higher in DS than controls or MR persons. The findings are consistent with those seen in DS brains.