The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution

Abstract

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related to tumor invasion and metastasis. Thus far, only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated. The finding that the cDNA for the 37LRP is virtually identical to a cDNA encoding the ribosomal protein p40 has suggested that 37LRP is actually a component of the translational machinery, with no laminin-binding activity. On the other hand, a peptide of 20 amino acids deduced from the sequence of 37LR/p40 was shown to exhibit high laminin-binding activity. The evolutionary relationship between 23 sequences of 37LRP/p40 proteins was analyzed. This 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 evolutionary analysis of the sequence identified as the laminin-binding site in the human protein suggested that the acquisition of the laminin-binding capability is linked to the palindromic sequence LMWWML, which appeared during evolution concomitantly with laminin.

Eukaryote-specific extensions in ribosomal proteins of the small subunit: Structure and function

“…34 One striking example in this regard is the ribosomal Figure 2. Graphical representation of the conservation of small ribosomal subunit protein families between different domains of life (E: Eukarya, A: Archaea, and B: Bacteria; left pie chart).…”

“…This protein appears to have acquired a second function as a cell surface receptor for laminin (a component of extracellular matrices) specifically in the vertebrate lineage. 34 Post-translational modification (i.e., acetylation) of uS2 is a prerequisite for conversion of the monomeric 37 kDa uS2 (known also as laminin receptor precursor (37LRP)) to the mature dimeric 67 kDa laminin receptor (67LR). 34 Mature 67LR associates with the plasma membrane, and its C-terminal laminin-binding domain becomes accessible to extracellular ligands.…”

“…34 Post-translational modification (i.e., acetylation) of uS2 is a prerequisite for conversion of the monomeric 37 kDa uS2 (known also as laminin receptor precursor (37LRP)) to the mature dimeric 67 kDa laminin receptor (67LR). 34 Mature 67LR associates with the plasma membrane, and its C-terminal laminin-binding domain becomes accessible to extracellular ligands. 34 The laminin binding capacity was attributed to a specific palindromic sequence LMWWML (found exclusively in vertebrates) in the C-terminal extension of human uS2.…”

Role of Ribosomal Protein RPS2 in Controlling let-7a Expression in Human Prostate Cancer

“…Likewise, L37RP/p40, RPP-1, RPS3a, and RPS2 are upregulated in the cells and tumors expressing the tumor suppressor gene p53 (14). The L37RP/p40 protein has been identified as a precursor of the 67-kDa laminin receptor whose enhanced expression is associated with tumor invasion and metastatic potential (15,16). Thus, one possibility is that the ability of RPS2, L37RP/p40, or RPS3a expression to induce transformation may require the cooperative effect of additional oncogene signals.…”

Identification of Oncofetal Antigen/Immature Laminin Receptor Protein Epitopes That Activate BALB/c Mouse OFA/iLRP-Specific Effector and Regulatory T Cell Clones

“…One would think, therefore, that tumor cells would not thrive if they down-regulated OFA/iLRP to escape an anti-OFA/iLRP effector T cell response. On top of this, the sequence of OFA/iLRP is evolutionarily conserved to a very high degree (19,50). Murine and human OFA/iLRP differ by only a few amino acids of 295 total in the protein.…”