| Popis: |
Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved kinase that is activated in response to growth factors and viral stimuli to influence cellular growth and proliferation. The serine/threonine kinase, S6K1 which is a downstream effector of phosphatidylinositol 3- kinase / Akt pathway, is frequently activated in certain types of cancers. S6K1 acts as an actin filament cross linking and as a Rho family of GTPase activating protein. We here present the evidence for domain specific interaction of S6 kinase 1 (S6K1) with filamentous actin or F actin. We show for the first time that [∆NH2-146 / ∆CT240 a. acid] region of S6K1 is actually responsible for its discrete binding to F actin. We also provide evidence that the binding of S6K1 to filamentous actin is phosphorylation independent and not facilitated by any other protein rather direct interaction and we couldn’t observe any interaction of S6K1 for monomeric actin (G actin) .By a time course experiment, we could found that the presence of S6K1 did not affect the kinetics of spontaneous actin polymerization but it enforces stability in F actin by cross linking it and rendering it more stable in the form of multifilament bundled actin. Using electron microscopy we found that these closely apposed bundles were often slightly curved, suggesting flexible cross linking. We further observe that S6 kinase 1 continued to exhibit sensitivity towards filamentous actin that remained unaffected by deletions compromised for [∆NH2-146 / ∆CT104] or [∆NH2-46] / ∆CT104] [∆NH2-146] or [∆NH2-46] or [∆CT104] . By computational study we found that [∆NH2-146 / ∆CT240 a. acid] region of S6K1 is rich in hydrophobic amino acids and has predominant α helical and coiled coil structure which serves as a structural basis for some of the actin binding proteins. These data together with the ability of the S6K1 to bind to F actin indicate that binding is phosphorylation independent, direct and facilitated by the [∆NH2-146 / ∆CT240 a. acid] region of S6K1. |
