Signal transduction cascades protein kinases

Protein kinases are central to many signal-transduction pathways. Protein kinases are central to all three signal-transduction pathways described in this chapter. In the epinephrine-initiated pathway, cAMP-dependent protein kinase (PKA) lies at the end of the pathway, transducing information represented by an increase in cAMP concentration into covalent modifications that alter the activity of key metabolic enzymes. In the insulin- and EGF-initiated pathways, the receptors themselves are protein kinases and several additional protein kinases participate downstream in the pathways. Signal amplification due to protein kinase cascades are common features of each of these pathways and many others. Furthermore, protein kinases often phosphorylate multiple substrates, including many not considered herein, and by this means are able to generate a diversity of responses. 

Pierce, R.C., Pierce-Bancroft, A.F., Prasad, B.M. Neurotrophin-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/Mitogen-activated protein kinase signal transduction cascade. J. Neurosci. 19 8685, 1999. 

Intracellular Signal Transduction the Protein Cascades of the MAP Kinase Pathways... 

This review will focus on enzymes converting sterols, but will not deal with proteins representing elements of signal transduction cascades, i.e. kinases or receptors. 

The A3 Receptor and the Mitogen-Activated Protein Kinases (MAPKs) Signal Transduction Cascade... 

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Despite this complexity, most integrins share two, key interrelated functions first, to promote the assembly and organization of the actin cytoskeleton [122, 123] and second, to regulate signal transduction cascades [124-126], Spanning the cell membrane, these subunits serve as a communication pathway, linking the actin cytoskeleton and intracellular cytoplasmic proteins involved in focal adhesion complexes (FACs) with the cell s dynamic extracellular environment (Fig. 8) [127-130]. There are at least 50 distinct proteins known to be involved in FACs. Actin [131], vinculin, talin, tensin, a-actinin, and filamin provide a structural role, while focal adhesion kinase [132], integrin-linked kinase, Src-family kinase, PINCH, paxillin... 

How elicitors affect JA biosynthesis and how the JA signal is transduced to affect gene expression is largely unknown. Several reports have implicated the activation of a wound-responsive MAPK cascade upstream of JA biosynthesis [61-63]. Downstream of the ODA pathway there are also one or more protein kinases involved in transduction of the JA signal [64]. A protein kinase (cascade) ultimately changes the activity of transcription factors, which regulate the... 

Extracellular epinephrine (adrenaline) (from the adrenal medulla) activates /33-adrenergic receptors on fat cells to induce the breakdown of triacylglycerols to free fatty acids and glycerol. The intracellular enzyme involved in this process, hormone-sensitive lipase, is activated by protein kinase A. What are the key elements of the signal transduction cascade ... 

Althou the role of the MAP kinase phosphorylation cascade in the control of cell growth and cellular proliferation is undisputed, other pathways and pathway ramifications contribute to that control. This requires communication between signal transduction pathways. MAP kinase also seems to play a part in pathway interconnections, for example in connecting signals from G-protein-coupled receptors with signals from growth-factor-activated receptors (discussed in Chapter 5). 

---