Paxillin LD motifs may define a new family of protein recognition domains

Abstract

Cells assemble protein networks through regions of protein recognition that are found in numerous proteins as conserved peptide motifs. This allows for the specific and efficient communication of signals derived from both extracellular and intracellular sources 1 . A subset of scaffolding proteins has emerged whose members are composed principally of these discrete protein-protein interaction motifs 2 . Paxillin is one of these molecular adaptor proteins that functions primarily at focal adhesions.Focal adhesions are multi-molecular complexes at sites of integrin-extracellular matrix ligation 3 . These assemblies are multi-potent in terms of transducing extracellular and intracellular cues 4 , and appear to be a point of convergence of growth factor and integrin signaling 5 .

SLK-mediated phosphorylation of paxillin is required for focal adhesion turnover and cell migration

“…This sequence homology translates into a leucine and aspartic acid-rich consensus sequence, LDXLLXXL, after which this domain was named [66]. This sequence has been found repeated four times within the N-terminus of the paxillin protein, defining LD motifs 1, 2, 4 and 5 [66,100,101]. The fifth LD domain, denoted by LD3 and encoded by the highly divergent exon 5, was later proposed by Tong et al in 1997 [66].…”

Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth

“…One of the conserved sequence elements (LDDILQHV, residues 388-395 in DLC-3a) is similar to the consensus LD motif (LDXLLXXL) found in paxillin and other signaling proteins, which mediates the binding of paxillin to vinculin and focal adhesion kinase (Brown et al, 1998). Downstream of this motif in human DLC-3 is an E80 amino acid insertion enriched in proline, alanine and glutamine residues, which has relatively low homology with the mouse sequence and is missing from chicken, frog, fish and marsupial DLC-3 sequences (not shown).…”

Paxillin Associates with Poly(A)-binding Protein 1 at the Dense Endoplasmic Reticulum and the Leading Edge of Migrating Cells

“…The recruitment of protein complexes to paxillin can be ascribed, in certain cases, to the association of individual LD domains with specific sequences in the protein ligand, termed the paxillin binding subdomain (31). To determine whether individual LD domains were capable of interacting with PABP1, LDs 1, 2, 4, and 5 were expressed as GST fusion proteins and incubated with either cell lysates or recombinant His-PABP1.…”