The Tec family tyrosine kinase Itk is critical for efficient signaling downstream of the TCR. Biochemically, Itk is directly phos-phorylated and activated by Lck. Subsequently, Itk activates phospholipase C-␥1, leading to calcium mobilization and extracel-lular signal-regulated kinase/mitogen-activated protein kinase activation. These observations suggested that Itk might play an important role...

Alternative splicing is an important mechanism of generating protein diversity and accelerated genome evolution. The mode of the selection acting in constitutive, major alternative and minor alternative regions of human genes is different. Whereas constitutive and major alternative regions tend to evolve under negative (stabilizing) selection, alternatively spliced exons from minor isoforms exp...

Interest in mismatched transplantation arises from the fact that a suitable one-haplotype mismatched donor is immediately available for virtually all patients, particularly for those who urgently need an allogenic transplant. Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres hav...

Apoptosis is a form of programmed cell death crucial for development, homeostasis, immunity, spermatogenesis, and prevention of cancer. Positive selection acting on mammalian apoptosis related genes targets protein interfaces that interact with pathogens and also elements of signaling complexes. Selection appears primarily to be driven by the immune/defense related function of these genes. More...

We describe the development of a novel positive-selection vector, RHP-AmpS, that is suitable for seamless cloning and high-level protein expression in Escherichia coli. In this vector, beta-lactamase (Bla) was rendered nonfunctional by replacing the codon for the C-terminal amino acid of the beta-lactamase gene (bla) with a stop codon. Insertion of a target gene in the correct orientation (tail...

As a new slant on T lymphocyte repertoire selection, we have examined batteries of TCR sequences in thymi from transgenic mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiating thymocytes expressing a set of particular TCR through the positive selection process. Subtly different TCR sequences can promote different maturation pathways and commitme...

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of natural selection in humans has largely been restricted to comparing individual candidate genes to theoretical expectations. The advent of genome-wide sequence and polymorphism data brings fundamenta...

We have isolated a limited set of cDNAs that limit cell proliferation using a unique assay based on the dilution of a lipophilic fluorescent dye as transfected cells divide. The identification of growth-inhibitory factors has been limited by the lack of a strong assay for growth inhibitors. A growth-inhibited cell does not grow and so is at a selective disadvantage in vitro when compared with a...