Cells protein phosphorylation

The arachidonic acid cascade takes part in a large number of functional interactions with other intracellular second messenger systems. As one would expect from their universal regulatory functions in the physiology of mammalian cells, protein phosphorylation and dephosphorylation play a major part in modulating arachidonate mobilization. Two multifunctional (and ubiquitous) protein kinases, PKC and PKA, have been studied extensively in this regard. 

Benjamin, W. B., and Singer, I., 1975, Actions of insulin, epinephrine, and dibutyryl cyclic adenosine 5 -monophosphate on fat cell protein phosphorylations. Cyclic adenosine 5 -monophosphate dependent and independent mechanisms. Biochemistry 14 3301. 

The abundance of many protein kinases in cells is an indication of the great importance of protein phosphorylation in cellular regulation. Exactly 113 protein kinase genes have been recognized in yeast, and it is estimated that the human genome encodes more than 1000 different protein kinases. Tyrosine kinases (protein kinases that phosphorylate Tyr residues) occur only in multicellular organisms (yeast has no tyrosine kinases). Tyrosine kinases are components of signaling pathways involved in cell-cell communication (see Chapter 34). 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Protein phosphorylation-dephosphorylation is a highly versatile and selective process. Not all proteins are subject to phosphorylation, and of the many hydroxyl groups on a protein s surface, only one or a small subset are targeted. While the most common enzyme function affected is the protein s catalytic efficiency, phosphorylation can also alter the affinity for substrates, location within the cell, or responsiveness to regulation by allosteric ligands. Phosphorylation can increase an enzyme s catalytic efficiency, converting it to its active form in one protein, while phosphorylation of another converts it into an intrinsically inefficient, or inactive, form (Table 9—1). 

III. ROLE OF PROTEIN PHOSPHORYLATION IN GERM CELL DIFFERENTIATION... 

Observations from various systems, including yeast, suggest that phosphorylation and dephosphorylation of proteins play important roles in the mitotic and meiotic cell cycles and the differentiation of germ cells. Extracts from mitotic HeLa cells contained phosphoproteins also present in other mitotic and meiotic cell types, but not in interphase cells (Davis et al., 1983). Exposure of Xenopus oocytes to progesterone results in a burst of protein phosphorylation shortly before GVBD (Mailer et al.,... 

Clarke, P. R., and Karsenti, K. (1991). Regulation of p34cprotein kinase new insights into protein phosphorylation and the cell cycle. J. Cell Sci. 100 409-414. 

Post-translational modification of proteins plays a critical role in cellular function. For, example protein phosphorylation events control the majority of the signal transduction pathways in eukaryotic cells. Therefore, an important goal of proteomics is the identification of post-translational modifications. Proteins can undergo a wide range of post-translational modifications such as phosphorylation, glycosylation, sulphonation, palmitoylation and ADP-ribosylation. These modifications can play an essential role in the function of the protein and mass spectrometry has been used to characterize such modifications. 

Kaufmann H et al. Influence of low temperature on productivity, proteome and protein phosphorylation of CHO cells. Biotechnol Bioeng 1999 63 573-682. Kristensen DB et al. Analysis of the rat dermal papilla cell proteome. Exp Dermatol 1999 8 339-340. 

Zappacosta, F., Collingwood, T.S., Huddleston, M.J., and Annan, R.S. (2006) A quantitative results-driven approach to analyzing multisite protein phosphorylation. Mol. Cell. Proteomics 5(11), 2019-2030. 

Most of the effects of cyclic AMP on cell function are mediated via protein phosphorylation 375... 

Cellular signals converge at the level of protein phosphorylation pathways. Individual intracellular messenger pathways, such as cAMP, Ca2+ and MAPK pathways, are often drawn as distinct biochemical cascades that operate in parallel in the control of cell function. While this is useful for didactic purposes, it is now well established that these various pathways function as complex webs, with virtually every conceivable type of interaction seen among them. 

Upregulation of the cAMP pathway may be a common mechanism by which a number of neuronal cell types respond to chronic opiates and develop tolerance and dependence (see Ch. 56). There is also evidence that similar mechanisms involving alterations in the cAMP second-messenger and protein phosphorylation pathway may mediate aspects of addiction to other types of drugs of abuse, for example, cocaine and alcohol [66],... 

Hunter, T. Protein kinases and phosphatases the yin and yang of protein phosphorylation and signaling. Cell 80 225-236,1995. 

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