Cloning and characterization of novel CIS family genes

Masaaki Masuhara, Hiroshi Sakamoto, Akira Matsumoto, Ritsu Suzuki, Hideo Yasukawa, Kaoru Mitsui, Toru Wakioka, Shyu Tanimura, Atsuo Sasaki, Hiroyuki Misawa, Masahiro Yokouchi, Motoaki Ohtsubo, Akihiko Yoshimura

研究成果: Article査読

216 被引用数 (Scopus)

抄録

We have reported two JAK-signaling modulators, CIS (cytokine-inducible SH2 protein) and JAB (JAK2 binding protein), which are structurally related. Here we cloned three additional CIS family genes (CIS2, CIS3, and CIS4) on the basis of an expression sequence tag (EST) database search. We also found at least two additional candidates of this gene family in the database. These genes were induced by erythropoietin and granulocyte-macrophage colony stimulating factor in certain hematopoietic cell lines. The SH2 domain and a C-terminal 40 amino acid region, designated the CIS homology domain (CH domain), are highly conserved in this family, while the N-terminal regions of these proteins share little similarity. A yeast two-hybrid assay and in vitro and in vivo binding assays revealed that in addition to JAB, CIS3 bound to the JAK2 tyrosine kinase domain (JH1), although the interaction of CIS3 with the JAK2-JH1 domain was much weaker than that of JAB. Transient expression of JAB and CIS3, but not other CISs, strongly inhibited leukemia inhibitory factor (LIF)-induced STAT3-reporter gene activation in 293 cells. Furthermore, constitutive overexpression of JAB and CIS3 in M1 leukemia cells prevented LIF-induced differentiation and growth arrest. Although the physiological function remains to be investigated, CIS family genes could play a role in the negative regulation of cytokine signaling by interacting with specific targets.

本文言語English
ページ(範囲)439-446
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
239
2
DOI
出版ステータスPublished - 1997 10月 20
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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