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Gene Review

RIPK4  -  receptor-interacting serine-threonine...

Homo sapiens

Synonyms: ANKK2, ANKRD3, Ankyrin repeat domain-containing protein 3, DIK, NKRD3, ...
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Disease relevance of RIPK4

  • Transitional carcinomas of the urinary bladder were examined immunohistochemically for keratin proteins with the use of polyclonal antiserum (TK, 41-65 kDa) and 3 monoclonal antibodies (KL 1, 55-57 kDa; PKK 1, nos. 19, 18, 8; and K 8.12, nos. 16, 13) [1].
  • Immunohistochemically, the cytoplasm of numerous cells of the squamous cell carcinoma component was stained with anti-cytokeratin (PKK 1) and the cytoplasmic membrane with anti-epithelial membrane antigen (EMA) [2].

High impact information on RIPK4

  • Protein kinase C-associated kinase (PKK, also known as RIP4/DIK) activates NFkappaB when overexpressed in cell lines and is required for keratinocyte differentiation in vivo [3].
  • Catalytically inactive PKK mutants that block phorbol ester-induced NFkappaB activation do not interfere with, but unexpectedly enhance, the activation of NFkappaB by these two mitogen-activated protein kinase kinase kinases [3].
  • The human homolog of PKK has over 90% identity to its murine counterpart, has been localized to chromosome 21q22.3, and is identical to the PKCdelta-interacting kinase, DIK (Bahr, C., Rohwer, A., Stempka, L., Rincke, G., Marks, F., and Gschwendt, M. (2000) J. Biol. Chem. 275, 36350-36357) [4].
  • Expression of DIK at the mRNA and protein level could be demonstrated in several cell lines [5].
  • DIK was shown to exhibit protein kinase activity toward autophosphorylation and substrate phosphorylation [5].

Biological context of RIPK4


Anatomical context of RIPK4

  • Here we explore the consequences of a null mutation in PKK with respect to the generation of peripheral B cell lineages and the activation of NFkappaB [6].
  • Intercalated duct cells of normal salivary glands reacted with RPN 1164, RPN 1165, K 4.62 and K 8.13 monoclonal antibodies, which indicates the presence of keratins 8 and 19; and ductal basal cells reacted with PKK 1, K 4.62 and K 8.12, suggesting nos [7].

Associations of RIPK4 with chemical compounds

  • Inspection for signature repeats in ncamp-1 and comparisons with histone-like peptides from different species indicated the presence of multiple lysine based motifs composed of AKKA or PKK repeats [8].
  • PKK clotting activity as well as the activity by a chromogenic substrate method (Chromozym PK) was less then 0.01 U/ml [9].


  1. Immunohistochemical expression of keratin proteins in urinary bladder carcinoma. Asamoto, M., Fukushima, S., Tatemoto, Y., Yamada, K., Fukui, S., Mori, M. Pathol. Res. Pract. (1989) [Pubmed]
  2. True pulmonary carcinosarcoma (squamous cell carcinoma and chondrosarcoma). A case report. Adachi, H., Morimura, T., Yumoto, T., Ikeda, M., Fukui, H. Acta Pathol. Jpn. (1992) [Pubmed]
  3. Protein kinase C-associated kinase can activate NFkappaB in both a kinase-dependent and a kinase-independent manner. Moran, S.T., Haider, K., Ow, Y., Milton, P., Chen, L., Pillai, S. J. Biol. Chem. (2003) [Pubmed]
  4. Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase. Chen, L., Haider, K., Ponda, M., Cariappa, A., Rowitch, D., Pillai, S. J. Biol. Chem. (2001) [Pubmed]
  5. DIK, a novel protein kinase that interacts with protein kinase Cdelta. Cloning, characterization, and gene analysis. Bhr, C., Rohwer, A., Stempka, L., Rincke, G., Marks, F., Gschwendt, M. J. Biol. Chem. (2000) [Pubmed]
  6. Protein kinase C-associated kinase is not required for the development of peripheral B lymphocyte populations. Moran, S.T., Cariappa, A., Liu, H., Boboila, C., Shi, H.N., Holland, P.M., Peschon, J.J., Pillai, S. Mol. Immunol. (2006) [Pubmed]
  7. Heterogeneity of keratin expression in epithelial tumor cells of adenolymphoma in paraffin sections. Orito, T., Shinohara, H., Okada, Y., Mori, M. Pathol. Res. Pract. (1989) [Pubmed]
  8. Molecular characterization of a novel pattern recognition protein from nonspecific cytotoxic cells: sequence analysis, phylogenetic comparisons and anti-microbial activity of a recombinant homologue. Evans, D.L., Kaur, H., Leary, J., Praveen, K., Jaso-Friedmann, L. Dev. Comp. Immunol. (2005) [Pubmed]
  9. CRM+ severe Fletcher factor deficiency associated with Graves' disease. Kyrle, P.A., Niessner, H., Deutsch, E., Lechner, K., Korninger, C., Mannhalter, C. Haemostasis (1984) [Pubmed]
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