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Gene Review

HCK  -  HCK proto-oncogene, Src family tyrosine...

Homo sapiens

Synonyms: Hematopoietic cell kinase, Hemopoietic cell kinase, JTK9, Tyrosine-protein kinase HCK, p59-HCK/p60-HCK, ...
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Disease relevance of HCK

  • Our findings add to the diversity of protein-tyrosine kinases that may serve specialized functions in hemopoietic cells, and they raise the possibility that damage to HCK may contribute to the pathogenesis of some human leukemias [1].
  • HCK is located on human chromosome 20 at bands q11-12, a region that is affected by interstitial deletions in some acute myeloid leukemias and myeloproliferative disorders [1].
  • Comparison of samples from patients taken prior to and following STI571 failure suggested that expression and/or activation of LYN/HCK occurs during disease progression [2].
  • Thermodynamic data, derived from isothermal titration calorimetry, for the binding of Hck SH3 to HIV-1 Nef show that the binding of Hck (KD = 1.5 microM) is approximately an order of magnitude tighter than those of other Src family kinases that were investigated (Fyn, Lck, and Src) [3].
  • Induction of CCL20 mRNA in HCE and HCK was also examined upon in vitro infection with HSV-1 [4].

High impact information on HCK

  • The human proto-oncogene HCK encodes two versions of a protein-tyrosine kinase, with molecular weights of 59,000 (p59hck) and 61,000 (p61hck) [5].
  • Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae [5].
  • The 57-kilodalton protein encoded by HCK resembles the product of the proto-oncogene c-src and is therefore likely to be a peripheral membrane protein [1].
  • Even at concentrations as high as 100 micrograms/ml (approximately 278 microM), this novel inhibitor did not affect the enzymatic activity of other protein tyrosine kinases, including JAK1, JAK3, HCK, epidermal growth factor receptor kinase, and insulin receptor kinase [6].
  • The human hemopoietic cell kinase (HCK) is a member of the src family of protein tyrosine kinases specifically expressed in myeloid cells and to a minor extent in B-lymphoid cells [7].

Biological context of HCK


Anatomical context of HCK


Associations of HCK with chemical compounds

  • However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees [13].

Regulatory relationships of HCK

  • In addition, in HCK cell over-expressing LEDGF, the levels of hINV mRNA and hINV protein are increased by four to five-fold [10].
  • HCK expression is up-regulated at the transcriptional level during myeloid differentiation of hematopoietic cells [7].

Other interactions of HCK

  • Sequence analysis and characterization of the intron/exon organization of the human HCK gene, encoding a hemopoietic-specific cell PTK of the src-related family, revealed a length of over 16 kb for the seven 3'-exons [14].
  • The genomic locus of the human hemopoietic-specific cell protein tyrosine kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron structure among human PTKs of the src family [14].
  • This regulation appears to be physiologically important, as over-expression of HCK with LEDGF increases the expression of the endogenous hINV gene and may provide new insight to understand the molecular mechanism of transcriptional regulation of this gene [10].


  1. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells. Quintrell, N., Lebo, R., Varmus, H., Bishop, J.M., Pettenati, M.J., Le Beau, M.M., Diaz, M.O., Rowley, J.D. Mol. Cell. Biol. (1987) [Pubmed]
  2. BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Donato, N.J., Wu, J.Y., Stapley, J., Gallick, G., Lin, H., Arlinghaus, R., Talpaz, M. Blood (2003) [Pubmed]
  3. RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef. Arold, S., O'Brien, R., Franken, P., Strub, M.P., Hoh, F., Dumas, C., Ladbury, J.E. Biochemistry (1998) [Pubmed]
  4. Corneal epithelial cells and stromal keratocytes efficently produce CC chemokine-ligand 20 (CCL20) and attract cells expressing its receptor CCR6 in mouse herpetic stromal keratitis. Shirane, J., Nakayama, T., Nagakubo, D., Izawa, D., Hieshima, K., Shimomura, Y., Yoshie, O. Curr. Eye Res. (2004) [Pubmed]
  5. Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae. Robbins, S.M., Quintrell, N.A., Bishop, J.M. Mol. Cell. Biol. (1995) [Pubmed]
  6. Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. Mahajan, S., Ghosh, S., Sudbeck, E.A., Zheng, Y., Downs, S., Hupke, M., Uckun, F.M. J. Biol. Chem. (1999) [Pubmed]
  7. The transcription factor Sp1 regulates the myeloid-specific expression of the human hematopoietic cell kinase (HCK) gene through binding to two adjacent GC boxes within the HCK promoter-proximal region. Hauses, M., Tönjes, R.R., Grez, M. J. Biol. Chem. (1998) [Pubmed]
  8. Platelet/polymorphonuclear leukocyte adhesion: a new role for SRC kinases in Mac-1 adhesive function triggered by P-selectin. Piccardoni, P., Sideri, R., Manarini, S., Piccoli, A., Martelli, N., de Gaetano, G., Cerletti, C., Evangelista, V. Blood (2001) [Pubmed]
  9. Human protein-tyrosine kinase gene HCK: expression and structural analysis of the promoter region. Lichtenberg, U., Quintrell, N., Bishop, J.M. Oncogene (1992) [Pubmed]
  10. Transactivation of involucrin, a marker of differentiation in keratinocytes, by lens epithelium-derived growth factor (LEDGF). Kubo, E., Fatma, N., Sharma, P., Shinohara, T., Chylack, L.T., Akagi, Y., Singh, D.P. J. Mol. Biol. (2002) [Pubmed]
  11. Identification of three RFLPs at the HCK locus on chromosome 20. Hollings, P.E., Morrison, M.J., Wells, E., Crossen, P.E. Hum. Genet. (1994) [Pubmed]
  12. Expression profile of protein tyrosine kinase genes in human osteoarthritis chondrocytes. Islam, S., Kermode, T., Sultana, D., Moskowitz, R.W., Mukhtar, H., Malemud, C.J., Goldberg, V.M., Haqqi, T.M. Osteoarthr. Cartil. (2001) [Pubmed]
  13. Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin. Lu, H., Chang, D.J., Baratte, B., Meijer, L., Schulze-Gahmen, U. J. Med. Chem. (2005) [Pubmed]
  14. The genomic locus of the human hemopoietic-specific cell protein tyrosine kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron structure among human PTKs of the src family. Hradetzky, D., Strebhardt, K., Rübsamen-Waigmann, H. Gene (1992) [Pubmed]
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