Figure 6 from The 67 kDa laminin receptor: structure, function and role in disease. | Semantic Scholar (2024)

Results show that 37LRP has some of the biological activities of 67LR, even prior to the conversion event, however, the conversion affects the sites of interaction with both laminin and heparan sulfate.

An in‐depth description of the complexity surrounding this multifaceted protein across functional, structural and pathological aspects is tried to convey.

A computational screening of a diversity library of small molecules using the recently solved 67LR crystal structure identified a lead compound that was characterized for its effects and could be the basis for the development of a new class of anti-cancer drugs, specifically targeting tumor invasion and metastasis.

Findings indicate that 37/67LR regulates proliferation and adhesion in normal intestinal epithelial cells independently of its known association with ribosomal function.

Recently, it is found that soluble laminin (laminin-1 isoform) as well as its YIGSR pentapeptide corresponding to the 67LR-binding sequence present in the β1-chain of laminationin, which can induce internalization of 67LR (Gopalakrishna et al., 2018).

Yeast two-hybrid screening using PEDF as bait discovered that the non-integrin 37/67-kDa laminin receptor (LR) is another PEDf receptor that mediates PEDFs angiogenesis inhibition.

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A phylogenetic analysis indicated that all of the protein sequences derive from orthologous genes and that the 37LRP is indeed a ribosomal protein that acquired the novel function of laminin receptor during evolution.

The data suggest that acylation of the precursor is the key mechanism in maturation of the 67 kD form, and the function of the membrane receptor is to stabilize the binding of laminin to cell surface integrins, acting as an integrin‐accessory molecule, although hom*ology of the gene encoding the receptor precursor with other genes suggests additional functions.

Data suggest that the 67LR is a heterodimer stabilized by strong intramolecular hydrophobic interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross‐reacting molecule, which is likely a palmitoylation process.

It is reported here that the 67LR molecule also functions in the proteolytic cleavage of laminin-1, a relevant event in basem*nt membrane degradation and tumor dissemination.

The results suggest that binding of laminin by cell surfacelaminin receptors induces synthesis of the 37LRP and mature 67LR, with a consequent delivery to the cell surface of more laminIn binding proteins for potentiated attachment of the melanoma cell to the basem*nt membrane during invasion and metastasis.

The interaction of the 67 kDa LBP with basem*nt membrane matrix appears to involve a complex series of events including multiple adhesive sites and tight regulation of cell surface expression.

Co-regulation of 67LR and α6 subunit expression, together with the physical association between the two receptors, supports the hypothesis that 67LR is an auxiliary molecule involved in regulating or stabilizing the interaction of laminin with the α6β4 integrin.

This study demonstrates that the 67LR, a cell membrane‐associated molecule exhibiting high affinity for the basem*nt membrane glycoprotein, laminin, is effectively shed by cancer cells, and could play an important role in modulating interactions between cancer cells and laminIn during tumor invasion and metastasis.

The binding site on laminin for the 67 kD metastasis-associated laminationin receptor is identified as a region on the long arm of laminIn close to the intersection of the four arms.

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