Disease relevance of LSP1

• LSP1 protein was detected in a wide range of leukaemias and lymphomas, particularly of B-cell origin, and in tumour cells in classical Hodgkin's disease [1].
• Of interest was the indication of a reciprocal relationship in the expression of LSP1 and ALK (anaplastic lymphoma kinase) proteins in patients with anaplastic large cell lymphoma [1].
• The motility of the melanoma cells is inhibited even at low levels of LSP1 expression [2].
• Leucocyte-specific protein (LSP1) in malignant lymphoma and Hodgkin's disease [3].
• Sf9 cells were infected with recombinant baculovirus expressing the cDNA of LSP1 truncates and mutants, and the morphology of infected Sf9 cells was documented by DIC optics [4].

High impact information on LSP1

• The protein p56lck (Lck) is a Src-like, lymphocyte-specific tyrosine kinase [5].
• Cross-linking of this lymphocyte-specific protein, designated TACI (transmembrane activator and CAML-interactor), on the surface of transfected Jurkat cells with TACI-specific antibodies led to activation of the transcription factors NF-AT, AP-1, and NFkappaB [6].
• A new technique of direct binding of radioactive DNA was used to screen a complementary DNA expression library from the BJAB cell line in lambda gt11 phage to derive molecular cDNA clones representing a putative B lymphocyte-specific octamer binding protein [7].
• Lymphoid enhancer-binding factor 1 (LEF-1) is a pre-B and T lymphocyte-specific nuclear protein that participates in the regulation of the T-cell antigen receptor (TCR) alpha enhancer by binding to the nucleotide sequence 5'-CCTTTGAA [8].
• CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane [9].

Biological context of LSP1

• Lymphocyte-specific protein 1, recently renamed leukocyte-specific protein 1 (LSP1), is an F-actin binding protein expressed in lymphocytes, macrophages, and neutrophils in mice and humans [10].
• Our data demonstrate that LSP1 is a negative regulator of neutrophil chemotaxis [10].
• The specificity of the monoclonal anti-LSP1 reagent was confirmed by expression cloning and transfection studies [1].
• LSP1 is localized to the internal surface of the plasma membrane, the cytoplasm, and NP-40-insoluble actin filaments and is thought to mediate cytoskeleton-driven responses in activated leukocytes that involve receptor capping, cell-cell interactions and cell motility [11].
• We propose that LSP1 plays a role in mediating cytoskeleton driven responses in lymphocytes such as receptor capping, cell motility, or cell-cell interactions [12].

Anatomical context of LSP1

• LSP1 modulates leukocyte populations in resting and inflamed peritoneum [10].
• Since its overexpression is implicated in the functional pathogenesis of a novel human neutrophil motile dysfunction and microfilamentous cytoskeletal abnormality (NAD 47/89), finding LSP1 in all human leukocytes suggests that it plays a role in regulating microfilamentous cytoskeleton structure and motile function in all leukocytes [13].
• This suggests that regulation of LSP1 expression in myeloid cells may be a functionally important event [13].
• By immunoblot, LSP1 is strongly expressed in PMN, less expressed in lymphocytes and monocytes (30-40% and 55-65% of the PMN level, respectively) [13].
• The presence of LSP1 protein in medullary thymocytes, but only in scattered cortical thymocytes, provided additional evidence for heterogeneity of expression in T cells [1].

Associations of LSP1 with chemical compounds

• LSP1(-) neutrophils demonstrate an enhanced chemotactic response in vitro to N-formyl methionyl-leucyl-phenylalanine (FMLP) and to the C-X-C chemokine, KC, indicating that their enhanced influx into the peritoneum may be a result of increased motility [10].
• As the anti-LSP1 reagent used in the present study recognizes a formalin-resistant epitope it should be of considerable value in the diagnosis of routinely fixed material [1].
• Mouse LSP1 protein contains 330 amino acids and contains an NH2-terminal acidic domain of approximately 177 amino acids [12].
• Mock transfectants without LSP1 (U937(-)) and cell lines with LSP1 levels similar to those of monocytes (U937(+)) or 4-fold those of monocytes (U937(+)) express LSP1 as indicated and express other actin-binding proteins at normal levels before or after monocytic induction (MI) with dibutyryl cyclic adenosine monophosphate [14].
• The C-terminal domains of the mouse and human LSP1 proteins are highly conserved and include several conserved, putative serine/threonine phosphorylation sites [15].

Physical interactions of LSP1

• Lymphocyte-specific Ca2+-binding protein LSP1 is associated with the cytoplasmic face of the plasma membrane [16].

Regulatory relationships of LSP1

• The lymphocyte-specific tyrosine protein kinase p56lck is endocytosed in Jurkat cells stimulated via CD2 [17].

Other interactions of LSP1

• Furthermore, the strong expression of LSP1 in classic Hodgkin's disease, contrasting with its heterogeneous expression in ALK-negative anaplastic lymphomas, may help to distinguish the latter lymphomas from patients with tumour cell-rich Hodgkin's disease [3].
• Human lymphocyte-specific protein 1 (LSP1) is an F-actin binding protein, which has an acidic N-terminal half and a basic C-terminal half [18].
• The results suggest cooperation between the caldesmon-like domains and the villin headpiece-like domains are required for the hair-forming activity of human LSP1 in cells [4].
• Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma [19].
• The lymphocyte-specific tyrosine kinase p56lck is physically associated with CD4 and is brought into close proximity of the intracellular domain of the antigen receptor by CD4 recognition of the major histocompatibility complex during antigen presentation. p56lck activation enhances and may be essential for antigen receptor signaling [20].

Analytical, diagnostic and therapeutic context of LSP1

• By immunoblot and Northern blot, LSP1 is minimally expressed in U-PLB985 and U-HL60 (< 10% of the PMN level) and is weakly expressed in the B lymphoid cell line Daudi, but is not expressed in the pro-B, pre-B, T lymphoid cell lines tested, U-U937 or MI-U937 [13].
• Immunohistochemistry and three-color flow cytometry analysis of fetal or postnatal thymocytes revealed that LSP1 was increasingly expressed during intrathymic human T-cell maturation [11].
• Site-directed mutagenesis of the basic amino acids in the KRYK (VI) or KYEK (VII) sequences to acidic amino acids create mutants that bind F-actin with lower affinity than full-length wild-type LSP1 [18].
• Immunoprecipitation of LSP1 protein from 32P-orthophosphate-loaded cells show that both the mouse and human LSP1 proteins are phosphoproteins [15].
• To define the hair-forming domains of LSP1, the relationship to the known F-actin binding domains, and binding domain interactions, LSP1 truncates, which include or exclude the different F-actin binding domains, were created by PCR [4].

References