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Hormonal control of the phosphorylation of histones, HMG proteins and other nuclear proteins
Abstract:
Hormone-dependent phosphorylation and dephosphorylation of nuclear proteins may play an important part in regulating nuclear function and specific gene expression. Some progress has been made in identifying specific nuclear proteins whose phosphorylation is affected by specific hormones; however, relatively little is known about the regulatory mechanisms involved, or about the molecular consequences of increased or decreased phosphorylation. It is suspected--but not yet proved--that cAMP-dependent effects on transcription are mediated at least partly by increases in nuclear cAMP-dependent protein kinase (A-kinase) activity, and consequent increases in the phosphorylation of specific chromatin proteins. In several instances, increased phosphorylation has been found to precede or correlate with cAMP-mediated induction of specific gene products. Several chromatin proteins are susceptible to cAMP-dependent phosphorylation in vivo, including histones H1 and H3, the high mobility group protein HMG 14 (which is preferentially associated with actively transcribed chromatin), and at least three other basic nonhistone proteins. The A-kinase phosphorylation sites of the majority of H1, H3 and HMG 14 molecules in chromatin appear to be inaccessible to A-kinase in vivo; nothing is known about the factors determining their accessibility, which may be tightly regulated and may vary significantly from cell to cell and tissue to tissue. Many hormone-induced changes in nuclear protein phosphorylation may be cAMP-independent. cAMP-independent mechanisms could involve a variety of nuclear enzymes including, for example, cGMP-dependent, Ca2+/calmodulin-dependent, Ca2+/phospholipid-dependent and polyamine-dependent protein kinases. So far, however, there is little solid evidence in support of a role for any specific cAMP-independent protein kinase in mediating hormonally induced increases in the phosphorylation of specific, identified nuclear proteins.