Carl E. Creutz, PhD
Calcium-dependent membrane-binding proteins and exocytosis
The Creutz research group is studying proteins involved in the transduction of signals in normal and transformed cells by calcium. For a number of years they have been studying a ubiquitous group of calcium-dependent, membrane-binding proteins that can promote membrane fusion in vitro. This group of proteins, collectively called annexins, includes synexin, calpactin, lipocortin, and several other members that have been proposed to mediate calcium-dependent events on membrane surfaces. A number of the annexins are prominent substrates for oncogenic or growth promoting tyrosine kinases and may be involved in signal transduction regulating cell growth. More recently they have extended the studies to the copines, another ubiquitous family of proteins that interact with membranes through a domain homologous to the calcium- and lipid-binding domain of protein kinase C. The copines have a protein-interaction domain that regulates the activities of certain "target" proteins and can recruit these target proteins to membrane surfaces. Most of the identified target proteins regulated by copines are components of signalling pathways, such as MEK1, a component of the MAP kinase signalling pathway, phosphatase 5, a regulator of endocrine receptors, a number of transcription factors that have oncogenic potential such as the myc oncogene, and regulators of cytoskeletal-membrane interactions that underlie intracellular organelle movements as well as cell migration and morphogenesis.