Identification of a Ten-Amino Acid Proline-Rich SH3 Binding Site

Abstract

The Src homology 3 (SH3) region is a small protein domain present in a very large group of proteins, including cytoskeletal elements and signaling proteins. It is believed that SH3 domains serve as modules that mediate protein-protein associations and, along with Src homology 2 (SH2) domains, regulate cytoplasmic signaling. The SH3 binding sites of two SH3 binding proteins were localized to a nine- or ten-amino acid stretch very rich in proline residues. Similar SH3 binding motifs exist in the formins, proteins that function in pattern formation in embryonic limbs of the mouse, and one subtype of the muscarinic acetylcholine receptor. Identification of the SH3 binding site provides a basis for understanding the interaction between the SH3 domains and their targets.

A novel human SPS1/STE20 homologue, KHS, activates Jun N-terminal kinase

“…Proteins containing these consensi are predicted to bind SH3-containing proteins and have proven to be regulatory for localization or activity (Bar-Sagi et al, 1993). Other proteins which contain this motif include the GTPase dynamin (Gout et al, 1993), the Rho-GAP 3BP-1 (Cicchetti et al, 1992(Cicchetti et al, , 1995Ren et al, 1993), and the guanine nucleotide exchange factor Sos1 . One other proline-rich kinase (not related to STE20), MAPKAP kinase 2, has been shown to bind the SH3 domain of c-Abl in a ®lter binding assay, but the relevance of this binding is unclear (Plath et al, 1994).…”

Disabled-2 (Dab2) is an SH3 domain-binding partner of Grb2

“…SH3 domains, a structure often found in signaling molecules, mediate protein-protein interactions by binding to proline-rich sequences in their binding partners (Ren et al, 1993).…”

New insights into protein‐tyrosine kinase receptor signaling complexes

“…This observation led to the suggestion that SH3 domains might function in the regulation of small GTP-binding proteins (Pawson & Gish, 1992;. By a combination of deletion mutagenesis and the use of short peptide sequences, the binding site for the Ab1 SH3 domain on 3BP-1 was localized to a short proline-rich region (Cicchetti et al, 1992;Ren et al, 1993). A 10-amino acid peptide containing the putative consensus sequence XPXXPPP9XP (where X is any amino acid and 9 is a hydrophobic amino acid) seems to be the minimum requirement for Ab1 SH3 domain binding to 3BP-l. A similar proline-rich sequence is found in 3BP-2, and a peptide containing this sequence is also capable of binding to SH3 domains .…”