NOREPINEPHRINE (NE) SUPPRESSES AND MAP KINASE KINASE (MEK1) INHIBITOR ENHANCES PROTEIN TYROSINE KINASE (PTK) ACTIVITY IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA). † 355

Protein Tyrosine Kinase plays a pivotal role in intracellular signal transduction pathways leading to complex expressions of cellular responses. NE is an important neurotransmitter engaging in varied arterial vascular pathophysiology. However, its post-receptor signalling pathway(s) in cerebral circulation is poorly understood. We have preliminarily studied regulatory aspects of NE on PTK of isolated MCA preparations of newborn lambs. PTK activities [PTK] were measured on soluble fraction [sPTK] and particulate fraction [pPTK] (100,000xgx1h) using a synthetic peptide (MW = 1,520) substrate RR-SRC with a known amino acid sequence (RRLIQDAEYAARG) surrounding the phosphorylation site in pp60src(Krebs, E.G., 1985). NE challenge(5μM) suppressed impressively both [sPTK](86%) and [pPTK](75%). In NE naive preparations, the enzyme activity was preferentially localized in [sPTK](≈ 160%/[pPTK]). Genistein(PTK inhibitor, 20 μM) stimulated [pPTK] over 40%. Interestingly, PD098059 (MEK1 inhibitor, 10 μM) robustly heightened[pPTK](80%). Taken together, it is concluded that NE exerted a suppressive effect on [PTK] and MEK1 inhibitor strengthened [pPTK]. Hence, it is proposed that interplay between PTK and MEK1 is implicated in NE-associated modification of intracellular machinery and that the link of the two signal transducing enzyme systems may present a characteristic biochemical basis for altered cerebral circulation and related clinical manifestations. (Inst Korean-American Studies;American Heart Association national council #95009270; Allegheny-Singer Res Inst #960181SCHC)

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Kim, S., Que, X., Russo, P. et al. NOREPINEPHRINE (NE) SUPPRESSES AND MAP KINASE KINASE (MEK1) INHIBITOR ENHANCES PROTEIN TYROSINE KINASE (PTK) ACTIVITY IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA). † 355. Pediatr Res 39, 62 (1996). https://doi.org/10.1203/00006450-199604001-00375

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