Protein tyrosine phosphorylation intracellular calcium regulation

Protein Tyrosine Phosphorylation and Regulation of Intracellular Calcium in Smooth Muscle Cells... 

Fig. 11.1 Activation of MAPK pathway by Angll and ET-1 in VSMC. Stimulation of Angll and ET-1 receptors through Gq/n activation enhances the activity of PLCp. Activated PLC 3 converts PIP2 to IP3 and diacylglycerol (DAG). IP3 elevates the concentration of intracellular calcium and DAG activates PKC. PKC and/or Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) activate nonreceptor (NR) and/or receptor (R) protein tyrosine kinases. Activation of these components signals the stimulation of Ras/Raf/MEK/ERKl/2 and p70 s6k. ERK1/2 and p70 s6k are translocated to nucleus and regulate nuclear events by activating transcription factors through phosphorylation.

The H2 receptor is a 359-amino-acid protein in humans. It has some features similar to the Hi protein (e.g., N-terminal glycosylation sites) and phosphorylation sites in the C-terminal. An aspartic acid residue in the third transmembrane loop appears to be critical to agonist and antagonist binding, and threonine/aspartate and tyrosine/aspartate couples in the fifth transmembrane domain appear to be important for interaction of the imidazole part of the histamine molecule. It is positively coupled via Gas to activate adenylyl cyclase for synthesis of cyclic adenosine monophosphate (cAMP) as a second messenger. In some systems, it is coupled through Gq proteins to stimulate phospholipase C. It appears in some cells that other processes, such as breakdown of phosphoinositides, control of intracellular calcium ion levels, and phospholipase A2 activity, can be regulated by other cAMP-independent pathways. 

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