Our results suggest that HD-PTP may be one of the adapters associated with LAT upon TCR activation and that it may modulate the endocytic trafficking of LAT/SLP-76 microclusters, thus downregulating the signaling output of the TCR. Further experiments are required to elucidate the molecular mechanisms controlled by HD-PTP in lymphocytes. In conclusion, we have identified Grb2 and GrpL as binding partners of HD-PTP. These interactions with adapters, which are essential for numerous signaling pathways, suggest that HD-PTP might have a role in the regulation of downstream events of a plethora of receptors. The nuclear membrane is composed of a two distinct lipid bilayers, and the inner nuclear membrane is composed of nucleoplasmic and transmembrane proteins. The lamins are intermediate filament proteins that form a scaffold intimately linked to the inner nuclear membrane where they provide shape and mechanical stability to the nucleus. This inner nuclear lamina is involved in multiple distinct cellular processes, including nuclear BYL719 assembly, apoptosis, signal transduction, transport, and chromosome segregation. The lamins contain a central a-helical coiled-coil rod domain that mediates the formation of the higher ordered structures that comprise the lamina. Lamins B1 and B2 are more highly expressed in mitotically active cells, and lamins A and C are expressed in post-mitotic cells. Lamins A and C are produced from the same gene and are identical for the first 566 amino acids. Over 300 different mutations associated with the LMNA gene have been described in a diverse list of overlapping phenotypes. Some of these phenotypes, especially those of striated muscle, represent a spectrum of disease. Known as laminopathies, these disorders include cardiac and skeletal myopathies, lipodystrophies, neuropathies, and premature aging syndromes. Point mutations, frameshift mutations, deletions, and nonsense mutations all contribute to the pathogenesis of the laminopathies, and most mutations are dominant. The mechanism by which LMNA mutations alter the function of the nuclear membrane and cause disease is still unclear. The nuclear lamina directly binds several key nuclear membrane proteins, including the SUN proteins, nesprins and emerin, as well as transcription regulators. The role of the nuclear lamina in regulating gene Semaxanib expression has been increasingly appreciated. Relocalization to the nuclear membrane has been shown to be sufficient to repress gene expression.