Endocr Pract. 1995 Nov-Dec;1(6):440-8. doi: 10.4158/EP.1.6.440.

Human Lp(a): regions in sequences of apoproteins similar to domains in signal transduction proteins.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

J Guevara, N V Valentinova, D Davison, J D Morrisett, J T Sparrow

PMID: 15251573 DOI: 10.4158/EP.1.6.440

Abstract

The major apoproteins of Lp(a)--apo(a) and apo B-100--are linked by only one intermolecular disulfide bond. This linkage has been suggested to be located between apo(a) Cys4057 and apo B-100 Cys3734. Several studies, however, have suggested other noncovalent interactions between different regions of apo(a) and apo B-100. One possible mechanism for these interactions may involve the apo(a) proline-rich interkringle regions that share sequence similarities with the proline-rich regions of Src homology 3 (SH3) domain-binding proteins such as 3BP-1. SH3 and SH2 domains, and their respective ligands, proline-rich regions, and phosphotyrosine motifs, are noncatalytic segments common to signal transduction proteins. Therefore, we used sequence comparison algorithms and molecular modeling programs to identify corresponding SH3 and SH2 candidate regions as well as potential phosphotyrosine sites in the apo B-100 sequence. Six SH2 and 16 SH3 candidate regions, along with 21 potential phosphotyrosine sites, are contained in the apo B-100 sequence. In Lp(a), these regions of apo B-100 may be involved in the noncovalent, protein-protein interactions between apo(a) and apo B-100. The presence of candidate SH3 and SH2 regions in apo B-100, and potential phosphotyrosine sites in apo B-100, apo(a), and apo A-I, suggests an alternative signaling pathway unrelated to the known B/E receptor.

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