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Gene Review

Hcls1  -  hematopoietic cell specific Lyn substrate 1

Mus musculus

Synonyms: AW213261, HS1, Hematopoietic cell-specific LYN substrate 1, Hematopoietic lineage cell-specific protein, Hs1, ...
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Disease relevance of Hcls1


High impact information on Hcls1

  • Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity [3].
  • We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable [3].
  • HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed [3].
  • Induction of tyrosine phosphorylation on a variety of cellular proteins, such as Vav, Cbl, and HS1, upon BCR cross-linking was also abolished in these B cells [4].
  • The 75-kD HS1 protein is highly tyrosine-phosphorylated during B cell antigen receptor (BCR)-mediated signaling [5].

Chemical compound and disease context of Hcls1


Biological context of Hcls1

  • Colocalization of HS1-green fluorescent protein with BCR was also correlated with tyrosine phosphorylation of HS1 [7].
  • These data indicate that Syk plays an important role in the translocation of HS1 into lipid rafts and may be responsible for actin assembly recruitment to rafts and subsequent antigen presentations [7].
  • Owing to low expression of HS1, WEHI-231-derived M1 cells, unlike the parental cells, are insensitive to BCR-mediated apoptosis [5].
  • Crossing the HS1-deficient mice with the mice harboring transgenes encoding alpha and beta chains of T-cell antigen receptor against a male H-Y antigen resulted in a progeny that demonstrated a significantly impaired ability of thymic negative selection [8].
  • The SH3 domain and the potential helix-turn-helix motif in LckBP1 suggest that this molecule may associate with various molecules and function as a DNA binding molecule [9].

Anatomical context of Hcls1

  • Furthermore HS1 was unable to translocate into lipid rafts in a chicken B cell line deficient in Syk [7].
  • Using unstimulated T lymphocytes, we further demonstrated that Lck binds to HS1 in vivo and that HS1 is tyrosine phosphorylated upon TCR stimulation [10].
  • These data show that disrupting HS1 has profoundly influenced the ability of erythroid cells to terminally differentiate [11].
  • The truncated HS1 also suppressed the development of erythroid colonies from fetal liver cells [11].
  • HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases [12].

Associations of Hcls1 with chemical compounds

  • Interestingly a murine HS1 mutant at the tyrosine residues Tyr388 and Tyr405 targeted by Syk failed to respond to BCR cross-linking for either translocation into lipid rafts or colocalization with BCR within cells [7].
  • Here we show that the hemopoietic-specific protein HS1 interacted directly with the SH3 domain of Lyn, via its proline-rich region [11].
  • Hydrocortisone-free cultures also synthesized heparan sulfate (HS) proteoglycans, including a cell-associated form (HS1), partially excluded from the TSK-400 column, and a secretory form (HS2), eluting at Kd = 0.15 [13].
  • Several distinct F-actin/PIP2-binding proteins, such as gelsolin, which severs and caps the plus-ends of actin filaments, or HS1, which cross-links actin filaments, have been shown to suppress v-Ha-Ras-induced malignant transformation when they are overexpressed [14].

Physical interactions of Hcls1


Other interactions of Hcls1

  • We previously identified a gene, LckBP1, which encodes a protein that binds to the Lck SH3 domain and is identical to murine SH1 [10].
  • Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect possible mechanisms of recruitment and activation of downstream molecules [10].
  • In two of five such escapees, alterations in either Syk, HS1, and/or Lyn were observed [15].
  • A truncated HS1, bearing the Lyn-binding domain, was introduced into J2E erythroleukemic cells to determine the impact upon responsiveness to erythropoietin [11].

Analytical, diagnostic and therapeutic context of Hcls1


  1. The protein tyrosine kinase substrate cortactin is differentially expressed in murine B lymphoid tumors. Miglarese, M.R., Mannion-Henderson, J., Wu, H., Parsons, J.T., Bender, T.P. Oncogene (1994) [Pubmed]
  2. Spi-1 transgenic mice develop a clonal erythroleukemia which does not depend on p53 mutation. Barnache, S., Wendling, F., Lacombe, C., Denis, N., Titeux, M., Vainchenker, W., Moreau-Gachelin, F. Oncogene (1998) [Pubmed]
  3. HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse. Gomez, T.S., McCarney, S.D., Carrizosa, E., Labno, C.M., Comiskey, E.O., Nolz, J.C., Zhu, P., Freedman, B.D., Clark, M.R., Rawlings, D.J., Billadeau, D.D., Burkhardt, J.K. Immunity (2006) [Pubmed]
  4. Impaired proliferation of peripheral B cells and indication of autoimmune disease in lyn-deficient mice. Nishizumi, H., Taniuchi, I., Yamanashi, Y., Kitamura, D., Ilic, D., Mori, S., Watanabe, T., Yamamoto, T. Immunity (1995) [Pubmed]
  5. Role of tyrosine phosphorylation of HS1 in B cell antigen receptor-mediated apoptosis. Yamanashi, Y., Fukuda, T., Nishizumi, H., Inazu, T., Higashi, K., Kitamura, D., Ishida, T., Yamamura, H., Watanabe, T., Yamamoto, T. J. Exp. Med. (1997) [Pubmed]
  6. Rapid tyrosine phosphorylation of HS1 in the response of mouse lymphoma L5178Y-R cells to photodynamic treatment sensitized by the phthalocyanine Pc 4. Xue, L.Y., He, J., Oleinick, N.L. Photochem. Photobiol. (1997) [Pubmed]
  7. Syk-mediated tyrosine phosphorylation is required for the association of hematopoietic lineage cell-specific protein 1 with lipid rafts and B cell antigen receptor signalosome complex. Hao, J.J., Carey, G.B., Zhan, X. J. Biol. Chem. (2004) [Pubmed]
  8. Antigen-receptor induced clonal expansion and deletion of lymphocytes are impaired in mice lacking HS1 protein, a substrate of the antigen-receptor-coupled tyrosine kinases. Taniuchi, I., Kitamura, D., Maekawa, Y., Fukuda, T., Kishi, H., Watanabe, T. EMBO J. (1995) [Pubmed]
  9. LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56lck. Takemoto, Y., Furuta, M., Li, X.K., Strong-Sparks, W.J., Hashimoto, Y. EMBO J. (1995) [Pubmed]
  10. Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect possible mechanisms of recruitment and activation of downstream molecules. Takemoto, Y., Sato, M., Furuta, M., Hashimoto, Y. Int. Immunol. (1996) [Pubmed]
  11. HS1 interacts with Lyn and is critical for erythropoietin-induced differentiation of erythroid cells. Ingley, E., Sarna, M.K., Beaumont, J.G., Tilbrook, P.A., Tsai, S., Takemoto, Y., Williams, J.H., Klinken, S.P. J. Biol. Chem. (2000) [Pubmed]
  12. HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases. Suzuki, Y., Demoliere, C., Kitamura, D., Takeshita, H., Deuschle, U., Watanabe, T. J. Immunol. (1997) [Pubmed]
  13. Bone marrow stromal proteoglycan heterogeneity: phenotypic variability between cell lines and the effects of glucocorticoid. Bentley, S.A., Kirby, S.L., Anklesaria, P., Greenberger, J.S. J. Cell. Physiol. (1988) [Pubmed]
  14. Treatment of Ras-induced cancers by the F-actin cappers tensin and chaetoglobosin K, in combination with the caspase-1 inhibitor N1445. Tikoo, A., Cutler, H., Lo, S.H., Chen, L.B., Maruta, H. The cancer journal from Scientific American. (1999) [Pubmed]
  15. Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy is established. Vitetta, E.S., Tucker, T.F., Racila, E., Huang, Y.W., Marches, R., Lane, N., Scheuermann, R.H., Street, N.E., Watanabe, T., Uhr, J.W. Blood (1997) [Pubmed]
  16. Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3. Takemoto, Y., Furuta, M., Sato, M., Kubo, M., Hashimoto, Y. Int. Immunol. (1999) [Pubmed]
  17. Molecular cloning and characterization of mouse HS1. Kitamura, D., Kaneko, H., Taniuchi, I., Akagi, K., Yamamura, K., Watanabe, T. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  18. Isolation and characterization of two parasitic protozoa from a Pacific harbor seal (Phoca vitulina richardsi) with meningoencephalomyelitis. Miller, M.A., Sverlow, K., Crosbie, P.R., Barr, B.C., Lowenstine, L.J., Gulland, F.M., Packham, A., Conrad, P.A. J. Parasitol. (2001) [Pubmed]
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