Tyrosinase (TYR) plays a critical role in cellular melanogenesis and, thus, has been the major target of pharmacological approaches for the control of skin pigmentation. This study examined an alternative molecular approach using TYR-small interfering RNA (siRNA) to control melanogenesis in the human melanocytes. Both the mRNA and protein levels of TYR were significantly lowered by TYR-siRNA tr...

The human tyrosinase gene TYR is a multifunctional reporter gene with potential use in photoacoustic imaging (PAI), positron emission tomography (PET), and magnetic resonance imaging (MRI). We sought to establish and evaluate a reporter gene system using TYR under the control of the Tet-on gene expression system (gene expression induced by doxycycline [Dox]) as a multimodality imaging agent. We...

Mutations of the critical and rate-limiting melanogenic enzyme tyrosinase (Tyr) result in hypopigmentation of the hair, skin and eyes. Two other related enzymes, Tyrp1 and Dct, catalyze distinct post-Tyr reactions in melanin biosynthesis. Tyr, Tyrp1 and Dct have been proposed to interact with and stabilize each other in multi-enzyme complexes, and in vitro, Tyr activity is more stable in the pr...

We have shown previously that axonal microtubules (MTs) are composite, consisting of two distinct domains that differ in their content of tyrosinated alpha-tubulin (tyr-tub). One domain is poor in tyr-tub and is situated at the minus end of the MT. The other domain is rich in tyr-tub and extends from the plus end of the tyr-tub-poor domain to the end of the MT. We have proposed that the spatial...

In Escherichia coli, tyrosyl-tRNA synthetase is known to esterify tRNA(Tyr) with tyrosine. Resulting d-Tyr-tRNA(Tyr) can be hydrolyzed by a d-Tyr-tRNA(Tyr) deacylase. By monitoring E. coli growth in liquid medium, we systematically searched for other d-amino acids, the toxicity of which might be exacerbated by the inactivation of the gene encoding d-Tyr-tRNA(Tyr) deacylase. In addition to the a...

Excess superoxide (O(2)(-)) and nitric oxide (NO) forms peroxynitrite (ONOO(-)) during cardiac ischemia reperfusion (IR) injury, which in turn induces protein tyrosine nitration (tyr-N). Mitochondria are both a source of and target for ONOO(-). Our aim was to identify specific mitochondrial proteins that display enhanced tyr-N after cardiac IR injury, and to explore whether inhibiting O(2)(-)/O...

The Shc adaptor protein contains two phosphotyrosine [Tyr(P)]binding modules--an N-terminal Tyr(P) binding (PTB) domain and a C-terminal Src homology 2 (SH2) domain. We have compared the ability of the Shc PTB domain to bind the receptors for nerve growth factor and insulin, both of which contain juxtamembrane Asn-Pro-Xaa-Tyr(P) motifs implicated in PTB binding. The Shc PTB domain binds with hi...