CREB protein

The critical feature of CREB protein activation is phosphorylation, which is required for CREB-mediated stimulation of transcription [16]. PKA phosphorylates CREB on a serine positioned at amino acid 133 in the CREB protein sequence. How phosphorylation activates... 

FIGURE 26-8 Immunohistochemical localization of cAMP response element-binding protein (CREB) in rat hippocampal neurons. Using a polyclonal antibody which recognizes both CREB and phospho-CREB protein, it is apparent that CREB protein is enriched in the nucleus of pyramidal cells of the CA1 region of the hippocampus. Scale bar is 30 pm. (Courtesy of Dr Stephen Ginsberg, Department of Pathology, University of Pennsylvania.)... 

Specific transcription factors bind to enhancer regions or, in a few cases, to silencers and mod-ciate the formation of the initiation complex, thus regulating the rate of initiation of transcription. Each gene contains a variety of enhancer or silencer sequences in its regulatory region. The exact combination of specific transcription factors available (and active) in a particular cell at a particular time determines which genes will be transcribed at what rates, because specific transcription factors are proteins, their expression can be cell-type specific.. Additionally, hormones may regulate the activity of some specific transcription factors. Examples include steroid receptors and the CREB protein. 

Control of gene expression through proteins like cAMP response element binding (CREB) protein (requires hours) Control of gene expression (requires hours)... 

Answen Q Proteins with SH2 domains might bind to the insulin receptor substrate-1 (IRS-1) to transmit signals from the insulin receptor, a tyrosine kinase type of receptor. PI-3 kinase is an example of an SH2 domain protein. SH2 domains are not involved in DNA binding (choices A and D). Examples of protein domains that bind DNA include zinc fingers (steroid receptors), leudne zippers (CREB protein), and helix-turn-helbc proteins (homeodomain proteins),... 

Exemplary is the regulation of the CREB protein of higher eucaryotes, displayed in Fig. 1.37. 

The CREB protein is a transcriptional activator for genes with cis-regulatory, cAMP-sensitive DNA elements (cAMP responsive elements, CREs). 

CREB protein = cAMP Response Element Binding Protein... 

Wilson, B. E., Mochon, E. and Boxer, L. M., 1996, Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis, Mol Cell Biol, 16, pp 5546-56. 

Barco A, Alarcon JM, Kandel ER (2002) Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture. Cell 108 689-703 Bear MF, Malenka RC (1994) Synaptic plasticity LTP and LTD. Curr Opin Neurobiol 4 389-99 Bender RA, Brewster A, Santoro B, Ludwig A, Hofmann F, Biel M, Baram TZ (2001) Differential and age-dependent expression of hyperpolarization-activated, cyclic nucleotide-gated cation channel isoforms 1 1 suggests evolving roles in the developing rat hippocampus. Neuroscience 106 689-98... 

As indicated in Chapters 5, 7 and 8, transcription can be switched on by a variety of signalling pathways. Thus, cAMP-mediated pathways generate phosphorylated CREB proteins that activate expression of particular proteins by binding to promoters called cAMP response elements (GREs). Similarly, Ca2+-dependent PKC activation results in phosphorylation of transcription factors that bind to and activate tetradecanoylphorbol ester response element (TRE) promoters. In the immune response bacterial lipopolysaccharide (LPS) and particular cytokines can switch on signalling pathways resulting in activation of transcription factors such as NFkB (Chapter 7) with resultant expression of proteins such as cytokines,... 

CRE, cAMP response element CREB protein, cAMP response element... 

Figure 8 Simplified diagram of a signaling cascade that involves NE, BDNF, and CREB after NE acts on the postsynaptic fi-noradrenergic receptor. NE couples to a G protein (Gas), which stimulates the production of cAMP from adenosine triphosphate (ATP). This reaction is catalyzed by adenylate cyclase (AC). cAMP activates protein kinase A (PKA). Inside the cell, PKA phosphorylates (P) the CREB protein, which binds upstream from specific regions of genes and regulates their expression. BDNF is one target of cAMP signaling pathways in the brain. CRE, cyclic AMP regulatory element ER, endoplasmic reticulum, [reprinted from Reference 76 with permission of the author and the publisher, Canadian Medical Association].

But how do changes in monoamine transmitter levels produce an eventual elevation of mood Raised neurotransmitter concentrations produce immediate alterations in postsynaptic receptor activation, leading to changes in second messenger (intracellular) systems and to gradual modifications in cellular protein expression. Antidepressants increase a cyclic AMP response-element binding (CREB) protein which in turn is involved in... 

---