Abstract: The invention relates to methods for pairwise sequencing of a double-stranded polynucleotide template, which methods result in the sequential determination of nucleotide sequences in two distinct and separate regions of the polynucleotide template. Using the methods of the invention it is possible to obtain two linked or paired reads of sequence information from each double-stranded template on a clustered array, rather than just a single sequencing read from one strand of the template.

Abstract: An isolated nucleic acid molecule is provided which encodes a mammalian signal mediator protein, HEF-1, involved in regulation of cellular morphological alterations. The encoded protein comprises an amino-terminal SH3 domain, an internal domain containing several SH2 binding motifs, and a carboxy-terminal effector domain that can induce pseudohyphal budding in yeast. The invention also provides the novel signal mediator protein, and antibodies thereto. These biological molecules are useful as research tools and as diagnostic and therapeutic agents in methods for the identification, detection and regulation of complex signaling events leading to morphological, potentially neoplastic, cellular changes.