• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jun 11, 1996; 93(12): 5991–5995.

Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain.


A novel human cDNA encoding a cytosolic 62-kDa protein (p62) that binds to the Src homology 2 (SH2) domain of p56lck in a phosphotyrosine-independent manner has been cloned. The cDNA is composed of 2074 nucleotides with an open reading frame encoding 440 amino acids. Northern analysis suggests that p62 is expressed ubiquitously in all tissues examined. p62 is not homologous to any known protein in the data base. However, it contains a cysteine-rich region resembling a zinc finger motif, a potential G-protein-binding region, a PEST motif, and several potential phosphorylation sites. Using T7-epitope tagged p62 expression in HeLa cells, the expressed protein was shown to bind to the lck SH2 domain. Deletion of the N-terminal 50 amino acids abolished binding, but mutagenesis of the single tyrosine residue in this region had no effect on binding. Thus, the cloned cDNA indeed encodes the p62 protein, which is a phosphotyrosine-independent ligand for the lck SH2 domain. Its binding mechanism is unique with respect to binding modes of other known ligands for SH2 domains.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Pawson T, Schlessingert J. SH2 and SH3 domains. Curr Biol. 1993 Jul 1;3(7):434–442. [PubMed]
  • Cohen GB, Ren R, Baltimore D. Modular binding domains in signal transduction proteins. Cell. 1995 Jan 27;80(2):237–248. [PubMed]
  • Eck MJ, Shoelson SE, Harrison SC. Recognition of a high-affinity phosphotyrosyl peptide by the Src homology-2 domain of p56lck. Nature. 1993 Mar 4;362(6415):87–91. [PubMed]
  • Songyang Z, Shoelson SE, Chaudhuri M, Gish G, Pawson T, Haser WG, King F, Roberts T, Ratnofsky S, Lechleider RJ, et al. SH2 domains recognize specific phosphopeptide sequences. Cell. 1993 Mar 12;72(5):767–778. [PubMed]
  • Weiss A, Littman DR. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. [PubMed]
  • Autero M, Saharinen J, Pessa-Morikawa T, Soula-Rothhut M, Oetken C, Gassmann M, Bergman M, Alitalo K, Burn P, Gahmberg CG, et al. Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase. Mol Cell Biol. 1994 Feb;14(2):1308–1321. [PMC free article] [PubMed]
  • Duplay P, Thome M, Hervé F, Acuto O. p56lck interacts via its src homology 2 domain with the ZAP-70 kinase. J Exp Med. 1994 Apr 1;179(4):1163–1172. [PMC free article] [PubMed]
  • Weber JR, Bell GM, Han MY, Pawson T, Imboden JB. Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor. J Exp Med. 1992 Aug 1;176(2):373–379. [PMC free article] [PubMed]
  • Gupta S, Weiss A, Kumar G, Wang S, Nel A. The T-cell antigen receptor utilizes Lck, Raf-1, and MEK-1 for activating mitogen-activated protein kinase. Evidence for the existence of a second protein kinase C-dependent pathway in an Lck-negative Jurkat cell mutant. J Biol Chem. 1994 Jun 24;269(25):17349–17357. [PubMed]
  • Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J. Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12338–12342. [PMC free article] [PubMed]
  • Cleghon V, Morrison DK. Raf-1 interacts with Fyn and Src in a non-phosphotyrosine-dependent manner. J Biol Chem. 1994 Jul 1;269(26):17749–17755. [PubMed]
  • Malek SN, Desiderio S. A cyclin-dependent kinase homologue, p130PITSLRE is a phosphotyrosine-independent SH2 ligand. J Biol Chem. 1994 Dec 30;269(52):33009–33020. [PubMed]
  • Joung I, Kim T, Stolz LA, Payne G, Winkler DG, Walsh CT, Strominger JL, Shin J. Modification of Ser59 in the unique N-terminal region of tyrosine kinase p56lck regulates specificity of its Src homology 2 domain. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5778–5782. [PMC free article] [PubMed]
  • Fuerst TR, Niles EG, Studier FW, Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. [PMC free article] [PubMed]
  • Kozak M. An analysis of vertebrate mRNA sequences: intimations of translational control. J Cell Biol. 1991 Nov;115(4):887–903. [PMC free article] [PubMed]
  • Gay P, Contamine D. Study of the ref(2)P locus of Drosophila melanogaster. II. Genetic studies of the 37DF region. Mol Gen Genet. 1993 Jun;239(3):361–370. [PubMed]
  • Campbell IG, Nicolai HM, Foulkes WD, Senger G, Stamp GW, Allan G, Boyer C, Jones K, Bast RC, Jr, Solomon E. A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. Hum Mol Genet. 1994 Apr;3(4):589–594. [PubMed]
  • Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993 Oct 28;365(6449):855–859. [PubMed]
  • Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994 Apr 15;8(8):869–884. [PubMed]
  • Ihle JN, Kerr IM. Jaks and Stats in signaling by the cytokine receptor superfamily. Trends Genet. 1995 Feb;11(2):69–74. [PubMed]
  • Lehel C, Olah Z, Jakab G, Anderson WB. Protein kinase C epsilon is localized to the Golgi via its zinc-finger domain and modulates Golgi function. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1406–1410. [PMC free article] [PubMed]
  • Chang EC, Barr M, Wang Y, Jung V, Xu HP, Wigler MH. Cooperative interaction of S. pombe proteins required for mating and morphogenesis. Cell. 1994 Oct 7;79(1):131–141. [PubMed]
  • Zhou G, Bao ZQ, Dixon JE. Components of a new human protein kinase signal transduction pathway. J Biol Chem. 1995 May 26;270(21):12665–12669. [PubMed]
  • Rechsteiner M. Regulation of enzyme levels by proteolysis: the role of pest regions. Adv Enzyme Regul. 1988;27:135–151. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...