Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression

Koji Murao, Hitomi Imachi, Wen M. Cao, Xiao Yu, Hiroshi Tokumitsu, Hiroyuki Inuzuka, Norman C W Wong, Margaret A. Shupnik, Ryoji Kobayashi, Toshihiko Ishida

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

TRH binds to a membrane receptor that activates several intracellular signaling pathways and increases transcription of the TSH and prolactin (PRL) genes. Although TRH induces TSH and PRL gene expression, the underlying mechanism is not clear. In this report we examined the role of the Ca 2+/calmodulin-dependent protein (CaM) kinase cascade in mediating TRH-stimulated transcription of TSH and PRL. RT-PCR and Western blot analysis were used to show that CaM kinase kinase (CaM-KK) and CaM IV (CaM-KIV) were present in rat anterior pituitary and its cell line GH3. Next, the effects of constitutively active CaM-KIV (CaM-KIVc) or its dominant negative mutant (CaM-KIVdn) on TSH and PRL promoter activity were tested in GH 3 cells. The results showed that either CaM-KIVc alone or an upstream kinase, CaM-KK, induced the activity of both TSH and PRL promoters. Exposure of GH3 cells to 100 μM TRH induced CaM-KIV activity within 5 min and, as expected, also increased both TSH and PRL promoter activity. In contrast, cells carrying the CaM-KIVdn isoform had suppressed TRH induction of both TSH and PRL promoter activity. These results indicate that the CaM-KK-CaM-KTV cascade probably plays an important role in TRH induction of TSH and PRL transcriptional activity in pituitary cells.

Original languageEnglish
Pages (from-to)4846-4852
Number of pages7
JournalEndocrinology
Volume145
Issue number11
DOIs
Publication statusPublished - Nov 2004
Externally publishedYes

Fingerprint

Calcium-Calmodulin-Dependent Protein Kinases
Thyrotropin-Releasing Hormone
Prolactin
Gene Expression
Phosphotransferases
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Protein Isoforms
Western Blotting
Cell Line
Polymerase Chain Reaction
Membranes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression. / Murao, Koji; Imachi, Hitomi; Cao, Wen M.; Yu, Xiao; Tokumitsu, Hiroshi; Inuzuka, Hiroyuki; Wong, Norman C W; Shupnik, Margaret A.; Kobayashi, Ryoji; Ishida, Toshihiko.

In: Endocrinology, Vol. 145, No. 11, 11.2004, p. 4846-4852.

Research output: Contribution to journalArticle

Murao, K, Imachi, H, Cao, WM, Yu, X, Tokumitsu, H, Inuzuka, H, Wong, NCW, Shupnik, MA, Kobayashi, R & Ishida, T 2004, 'Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression', Endocrinology, vol. 145, no. 11, pp. 4846-4852. https://doi.org/10.1210/en.2004-0544
Murao, Koji ; Imachi, Hitomi ; Cao, Wen M. ; Yu, Xiao ; Tokumitsu, Hiroshi ; Inuzuka, Hiroyuki ; Wong, Norman C W ; Shupnik, Margaret A. ; Kobayashi, Ryoji ; Ishida, Toshihiko. / Role of calcium-calmodulin-dependent protein kinase cascade in thyrotropin (TSH)-releasing hormone induction of TSH and prolactin gene expression. In: Endocrinology. 2004 ; Vol. 145, No. 11. pp. 4846-4852.
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