Soluble extracts of many mammalian tissues, including lung and spleen, contain Beta-galactoside binding lectins. Three were recently purified from rat lung with subunit Mrs 14,500, 18,000 and 29,000 (RL-14.5, RL-18 and Rl-29) and two were purified from human lung (HL-14 and HL-29). Previous work suggests that these lectins function at the cell surface or extracellularly by interacting with specific glycoconjugates. Our goal is to accumulate structural and functional information about these lectins which will lead to an understanding of their biological roles. THe biological studies will be done with lymphocytes because they have many practical advantages and contain both RL-14.5 and receptors for this lectin. These studies will contribute to a general understanding of endogenous lectin functions in the many tissues which contain them. We propose to: a. Identify relative binding of these endogenous lectins to a large panel of known mammalian glycoconjugates, to define their active sites and potential competitive interactions. b. Identify lymphocyte glycoproteins and glycolipids which act as receptors for these endogenous lectins, as judged by their binding properties. c. Examine the biological effects of these lectins. Initially we will continue our studies which show that exogenous RL-14.5 activates B or T lymphocytes (but only in conjunction with specific growth factors). Then we will determine if this endogenous lectin (which we find in virtually all B and most T lymphocytes) is secreted and involved in the lymphocyte activation which normally results from specific cell-cell interactions. d. Clone the genes for HL-14, HL-29 and related mammalian lectins. The genes will be used to deduce amino acid sequences; to determine if there are multiple forms of the lectins under different developmental control; and for functional studies using lymphocyte cell lines transformed with anti-sense DNA.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL038627-03
Application #
3354917
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1986-09-30
Project End
1991-09-29
Budget Start
1988-09-30
Budget End
1989-09-29
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Overall Medical
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Gitt, M A; Xia, Y R; Atchison, R E et al. (1998) Sequence, structure, and chromosomal mapping of the mouse Lgals6 gene, encoding galectin-6. J Biol Chem 273:2961-70
Gitt, M A; Colnot, C; Poirier, F et al. (1998) Galectin-4 and galectin-6 are two closely related lectins expressed in mouse gastrointestinal tract. J Biol Chem 273:2954-60
Gitt, M A; Wiser, M F; Leffler, H et al. (1995) Sequence and mapping of galectin-5, a beta-galactoside-binding lectin, found in rat erythrocytes. J Biol Chem 270:5032-8
Massa, S M; Cooper, D N; Leffler, H et al. (1993) L-29, an endogenous lectin, binds to glycoconjugate ligands with positive cooperativity. Biochemistry 32:260-7
Herrmann, J; Turck, C W; Atchison, R E et al. (1993) Primary structure of the soluble lactose binding lectin L-29 from rat and dog and interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence with bacterial and tissue collagenase. J Biol Chem 268:26704-11
Oda, Y; Herrmann, J; Gitt, M A et al. (1993) Soluble lactose-binding lectin from rat intestine with two different carbohydrate-binding domains in the same peptide chain. J Biol Chem 268:5929-39
Marschal, P; Herrmann, J; Leffler, H et al. (1992) Sequence and specificity of a soluble lactose-binding lectin from Xenopus laevis skin. J Biol Chem 267:12942-9
Cooper, D N; Massa, S M; Barondes, S H (1991) Endogenous muscle lectin inhibits myoblast adhesion to laminin. J Cell Biol 115:1437-48
Cooper, D N; Barondes, S H (1990) Evidence for export of a muscle lectin from cytosol to extracellular matrix and for a novel secretory mechanism. J Cell Biol 110:1681-91
Hinek, A; Wrenn, D S; Mecham, R P et al. (1988) The elastin receptor: a galactoside-binding protein. Science 239:1539-41

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