Src-homology 2 (SH2) domains are conserved, globular protein modules that mediate assembly of multicomponent signaling complexes. Phosphoproteins from the B-lymphoid cell line A20 were isolated by SH2 affinity chromatography; the peptide sequence from one of these proteins was used to molecularly clone several related complementary DNAs whose predominant protein product, p130(PITSLRE), is an abundant serine/threonine kinase with ubiquitous expression in murine tissues. The sequence of a previously described cyclin- dependent kinase homologue, p58(clk-1), is entirely contained within the p130(PITSLRE) sequence. Specific binding of p130(PITSLRE) to SH2 domains is mediated by a serine- and glutamic acid-rich cluster of amino acids in the N- terminal region. This interaction is dependent on serine/threonine phosphorylation but independent of tyrosine phosphorylation. Binding is inhibited by free phosphotyrosine and by a phosphotyrosine-containing peptide from polyoma middle T antigen, suggesting that the p130(PITSLRE) binding site in the SH2 domain overlaps the region that binds phosphotyrosine-containing peptides. Bacterially expressed p130(PITSLRE) fragments acquire the ability to bind an SH2 domain when phosphorylated in vitro with casein kinase II. A subset of casein kinase II phosphorylation sites may therefore constitute a phosphotyrosine-independent class of SH2 ligands.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Biological Chemistry|
|State||Published - Dec 1 1994|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology