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dc.contributor.authorCaelles, Carme-
dc.contributor.authorHennemann, Hanjo-
dc.contributor.authorKarin, Michael-
dc.identifier.citationMolecular and Cellular Biology 15(12): 6694-6701 (1995)en_US
dc.description8 pages, 7 figures.en_US
dc.description.abstractGHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)- and prolactin-expressing cells in the anterior pituitary. It was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA) phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain, thereby inhibiting its binding to the GH promoter. These results, however, are inconsistent with the physiological stimulation of GH production by the cAMP pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in living cells and although they stimulate the phosphorylation of GHF-1, the inhibitory phosphoacceptor site within the homeodomain is not affected. Instead, this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result, GHF-1 DNA binding activity is transiently inhibited during the M phase. This activity is regained once cells enter G1, a phase during which GHF-1 phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA binding Ser-382. As this site is conserved in all POU proteins, it appears that all members of this group are similarly regulated. A specific kinase activity distinct in its substrate specificity and susceptibility to inhibitors from the Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This novel activity could be involved in regulating the DNA binding activity of all POU proteins in a cell cycle-dependent manner.en_US
dc.description.sponsorshipThis study was supported by NIH grant DA38527 to M.K. C.C. was supported by a postdoctoral fellowship from the Fundacion Ramon Areces, and H.H. was supported by a Feodor Lynen postdoctoral fellowship from the Alexander von Humboldt Foundation.en_US
dc.format.extent697832 bytes-
dc.publisherAmerican Society for Microbiologyen_US
dc.titleM-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell cycle-regulated protein kinase inhibits DNA bindingen_US
dc.description.peerreviewedPeer revieweden_US
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