The egg peptide speract receptor is a transmembrane glycoprotein of about500 amino acids []. Topologically, it comprises a large extracellulardomain of about 450 residues, followed by a transmembrane domain and ashort cytoplasmic region of about 12 amino acids. The extracellulardomain contains 4 repeats of a well-conserved region, which spans 115amino acids and contains 6 conserved cysteines. A similar domain is alsofound towards the C terminus of macrophage scavenger receptor type I [],a membrane glycoprotein implicated in the pathologic deposition ofcholesterol in arterial walls during artherogenesis, and in the CD5glycoprotein, which acts as a receptor in regulating T-cell proliferation.The T1/Leu-1/CD5 glycoprotein is expressed at the surface membrane of allmature T cells. It has been implicated both in the proliferative response of activated T cells and in T-cell helper function []. Thecomplete amino-acid sequence of the T1 precursor has been deduced from cDNAclones. The protein contains a classical signal peptide; a 347-residue extracellular segment; a transmembrane region; and a 93-residue intra-cellular segment []. The extracellular region contains several cysteineresidues and comprises 2 speract receptor domains separated by a proline/threonine-rich region []. CD5 has been shown to function as a receptor,delivering co-stimulatory signals to T-cells, interacting specifically withthe cell-surface protein CD72 (Lyb-2 in mice) exclusive to B-cells [].
Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR []. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5 []. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules []. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction [, ].
