NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain

Yi Chi Su, Jiahuai Han, Shuichan Xu, Melanie Cobb, Edward Y. Skolnik

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Nck, an adaptor protein composed of one SH2 and three SH3 domains, is a common target for a variety of cell surface receptors. We have identified a novel mammalian serine/threonine kinase that interacts with the SH3 domains of Nck, termed Nck Interacting Kinase (NIK), This kinase is most homologous to the Sterile 20 (Ste20) family of protein kinases. Of the members of this family, GCK and MSST1 are most similar to MK in that they bind neither Cdc42 nor Rac and contain an N-terminal kinase domain with a putative C-terminal regulatory domain. Transient overexpression of NIK specifically activates the stress-activated protein kinase (SAPK) pathway. Both the kinase domain and C-terminal regulatory region of NIK are required for full activation of SAPK. NIK likely functions upstream of MEKK1 to activate this pathway; a dominant-negative MEK kinase 1 (MEKK1) blocks activation of SAPK by NIK, MEKK1 and NIK also associate in cells and this interaction is mediated by regulatory domains on both proteins. Two other members of this kinase family, GCK and HPK1, contain C-terminal regulatory domains with homology to that of NIK. These findings indicate that the C-terminal domain of these proteins encodes a new protein domain family and suggests that this domain couples these kinases to the SAPK pathway, possibly by interacting with MEKK1 or related kinases.

Original languageEnglish (US)
Pages (from-to)1279-1290
Number of pages12
JournalEMBO Journal
Volume16
Issue number6
DOIs
StatePublished - Mar 17 1997

Fingerprint

MAP Kinase Kinase Kinase 1
Heat-Shock Proteins
Protein Kinases
Phosphotransferases
src Homology Domains
Proteins
Chemical activation
Nucleic Acid Regulatory Sequences
Protein-Serine-Threonine Kinases
Cell Surface Receptors

Keywords

  • MEKK1
  • Nck interacting kinase
  • Ste20-related kinase
  • Stress-activated protein kinase

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. / Su, Yi Chi; Han, Jiahuai; Xu, Shuichan; Cobb, Melanie; Skolnik, Edward Y.

In: EMBO Journal, Vol. 16, No. 6, 17.03.1997, p. 1279-1290.

Research output: Contribution to journalArticle

Su, Yi Chi ; Han, Jiahuai ; Xu, Shuichan ; Cobb, Melanie ; Skolnik, Edward Y. / NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. In: EMBO Journal. 1997 ; Vol. 16, No. 6. pp. 1279-1290.
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