The 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution.
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.
Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
E
E
Ardini
G
G
Pesole
E
E
Tagliabue
A
A
Magnifico
V
V
Castronovo
M E
ME
Sobel
M I
MI
Colnaghi
S
S
Ménard
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009369:Neoplasms / Q000235:genetics; D010802:Phylogeny; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017474:Receptors, Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D007797:Laminin; D011498:Protein Precursors; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C086117:Rpsa protein, rat