Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains.
Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85alpha, phospholipase Cgamma1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding motifs were found to inhibit its association with c-Src, Fgr, and phospholipase Cgamma1 SH3 domains, but not the p85alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells.
Finan
P M
PM
Yamanouchi Research Institute, Littlemore Hospital, Oxford OX4 4XN, United Kingdom.
Soames
C J
CJ
Wilson
L
L
Nelson
D L
DL
Stewart
D M
DM
Truong
O
O
Hsuan
J J
JJ
Kellie
S
S
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D010738:Type C Phospholipases / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics / Q000378:metabolism*; D051316:Wiskott-Aldrich Syndrome Protein; D018909:src Homology Domains; D019061:src-Family Kinases
D011506:Proteins; D011518:Proto-Oncogene Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases; D010738:Type C Phospholipases