A cyclin-dependent kinase homologue, p130(PITSLRE), is a phosphotyrosine- independent SH2 ligand

S. N. Malek, S. Desiderio

Research output: Contribution to journalArticlepeer-review


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 languageEnglish (US)
Pages (from-to)33009-33020
Number of pages12
JournalJournal of Biological Chemistry
Issue number52
StatePublished - 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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