Abstract
Src homology 2 (SH2) domains are structural modules that function in the assembly of multicomponent signaling complexes by binding to specific phosphopeptides. The tetratricopeptide repeat (TPR) is a distinct structural motif that has been suggested to mediate protein-protein interactions. Among SH2-binding phosphoproteins purified from the mouse B cell lymphoma A20, a 150-kDa species was identified and the corresponding complementary DNA (cDNA) was molecularly cloned. This protein encoded by this cDNA, which we have termed p150TSP (for TPR-containing, SH2-binding phosphoprotein), is located predominantly in the nucleus and is highly conserved in evolution. The gene encoding p150TSP (Tsp) was mapped to chromosome 7 of the mouse with gene order: centromere-Tyr-Wnt11-Tsp-Zp2. The amino-terminal two-thirds of p150TSP consist almost entirely of tandemly arranged TPR units, which mediate specific, homotypic protein interactions in transfected cells. The carboxyl-terminal third of p150TSP, which is serine- and glutamic acid-rich, is essential for SH2 binding; this interaction is dependent on serine/threonine phosphorylation but independent of tyrosine phosphorylation. The sequence and binding properties of p150TSP suggest that it may mediate interactions between TPR-containing and SH2-containing proteins.
Highlights
Src homology 2 (SH2)1 domains are conserved structural modules of about 100 amino acid residues that have been identified in tyrosine kinases of the Src family and in more than 60 other proteins [1]
This interaction is mediated by a serine- and glutamic acid-rich region of p130PITSLRE and is likely to involve the same site in the SH2 domain that binds phosphotyrosine-containing peptides
The tetratricopeptide repeat (TPR) is a 34-amino acid motif found in proteins that function in diverse processes, including cell cycle control, transcriptional repression, protein transport, and protein dephosphorylation [10]
Summary
Src homology 2 (SH2) domains are conserved structural modules of about 100 amino acid residues that have been identified in tyrosine kinases of the Src family and in more than 60 other proteins [1]. In Bcr-Abl chimeras that are implicated in the pathogenesis of chronic myelogenous leukemia, the Bcr segment contains serine/threonine- and glutamic acid-rich regions that bind SH2 domains in a phosphorylation-dependent manner but independent of phosphotyrosine [6]. We described SH2 binding by the cyclin-dependent kinase homologue p130PITSLRE [9] This interaction is mediated by a serine- and glutamic acid-rich region of p130PITSLRE and is likely to involve the same site in the SH2 domain that binds phosphotyrosine-containing peptides. There is evidence that TPRs mediate interactions with non-TPR-containing proteins: the transcriptional repression protein SSN6 (Cyc8), for example, interacts with specific DNA-binding proteins by means of its TPR region [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
