EFFECT OF RANTES ON PROTEIN TYROSINE KINASE ACTIVITY (PTK) IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA) 2236

RANTES, β (C-C) subfamily of chemokine, is reported to be an important pro-inflammatory factor implicated in varied immuno-compromised pathophysiology. PTK plays a pivotal role in intracellular signal transduction pathways leading to a complex expression of cellular response(s). However, post-receptor signalling pathway(s) of RANTES in immuno-compromised cerebral circulation is poorly understood. We have preliminarily studied règulatory aspects of RANTES 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). rhRANTES (E. Coli-expressed) challenge (1.0 μg/ml) suppressed(≈180%)[pPTK]. In rhRANTES naive preparations, the enzyme activity was evenly distributed between the two compartments. Neutralizing polyclonal anti-rhRANTES antibody(100 μg/ml) enhanced [sPTK] by 30% while diminishing[pPTK](≈32%). Interestingly, genistein(20 μM;PTK inhibitor) pretreatment induced over 131% increase in [sPTK] with a concomitant decrease in[pPTK](≈9%). PD09859(MEK1 inhibitor, 10 μM) reduced [pPTK] by ≈10%. Taken together, it is concluded within the context of this experimental paradigm that rhRANTES exerted a suppressive effect on [pPTK] and genistein effected positively on [sPTK] challenged by rhRANTES. Hence, it is proposed that interplay between PTK and MEK1 is involved in RANTES associated modification of subcellular machinery and that the link of the two signal transducing enzyme systems may present a characteristic biochemical basis for immuno-compromised cerebral microcirculation and related clinical manifestations. (Supported in part by Institute for Korean-American Studies, and American Heart Association national council #95009270)

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Kim, S., Que, X., Russo, P. et al. EFFECT OF RANTES ON PROTEIN TYROSINE KINASE ACTIVITY (PTK) IN NEWBORN LAMB MIDDLE CEREBRAL ARTERIES (MCA) 2236. Pediatr Res 39, 375 (1996). https://doi.org/10.1203/00006450-199604001-02261

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