A role for SSeCKS, a major protein kinase C substrate with tumour suppressor activity, in cytoskeletal architecture, formation of migratory processes, and cell migration during embryogenesis

SSeCKS is a major protein kinase C substrate which has tumour suppressor ac tivity in models of src- and ras-induced oncogenic transformation. The mito genic regulatory activity of SSeCKS is likely manifested by its ability to bind key signalling proteins such as protein kinases C and A and calmodulin , and to control actin-based cytoskeletal architecture. Rat SSeCKS shares e xtensive homology with human Gravin, an autoantigen in myasthenia gravis th at encodes kinase scaffolding functions and whose expression pattern in fib roblasts and nerves suggests a role in cell motility. Here, we analyse the expression of SSeCKS and Gravin in rodent and human fibroblast and epitheli al cell lines using antibodies specific or crossreactive for SSeCKS or Grav in. SSeCKS expression was then analysed in developing mouse embryos and in adult tissues. In the foetal mouse, early SSeCKS protein expression (E10-11 ) is focused in the loose mesenchyme, luminal surface of the neural tube, n otochord, early heart and pericardium, urogenital ridge, and dorsal and ven tral sections of limb buds. In later stages (E12-14), SSeCKS is widely expr essed in mesenchymal cells but is absent in the spinal ganglia. By E15, SSe CKS expression is ubiquitous, although the staining pattern varies from bei ng striated within smooth muscle sarcomeres to filamentous in mesenchymal a nd select epithelial cells. In the adult mouse, SSeCKS staining is relative ly ubiquitous, with highest expression in the gonads, smooth and cardiac mu scle, lung, brain and heart. High expression is also detected in fibroblast s and nerve fibres as well as in more specialized cells such as glomerular mesangial cells and testicular Sertoli cells. SSeCKS expression in the rat testes correlates with the induction of puberty, and in mature mouse sperma tozoa, SSeCKS is found in peripheral acrosome membranes and in a helix-like winding pattern within the midsection. Periodic enrichments of SSeCKS are found in sperm midsections and in developing axons, suggesting a role in ar chitectural infrastructure. As with Gravin, high SSeCKS expression is absen t in most epithelial cells; however, in contrast to Gravin, SSeCKS is expre ssed in Purkinje cells, cardiac muscle, macrophages and hepatic stellate ce lls, indicating overlapping yet distinct patterns of tissue expression in t he SSeCKS/Gravin family. The data suggest roles for SSeCKS in the control o f cytoskeletal and tissue architecture, formation of migratory processes an d cell migration during embryogenesis.