A type II phosphatidylinositol 4-kinase associates with T cell receptor zeta chain in Con A stimulated splenic lymphocytes through tyrosyl phosphorylation-dependent mechanisms.
T cells show rapid reorganization of cytoskeleton in response to antigenic stimulation. The molecular mechanisms by which TCR-CD3 regulates actin cytoskeleton are not well defined. Here we show that a type II PtdIns 4-kinase associates with cytoskeletal fraction in splenic lymphocytes in response to Con A. Protein tyrosyl phosphorylation of type II PtdIns 4-kinase appears to be the mechanism for its association with cytoskeleton. Over-lay blots suggest that the enzyme binds to TCR-CD3 zeta chain in the cytoskeletal fraction. Anti-TCR-CD3 zeta antibodies competitively inhibit PtdIns 4-kinase association with TCR-CD3 zeta chain. Immunodepletion of TCR-CD3 zeta decreases PtdIns 4-kinase activity in the cytoskeletal fraction with a concomitant increase in PtdIns 4-kinase activity in anti-TCR-CD3 zeta immunoprecipitates. We propose that the association of type II PtdIns 4-kinase with TCR-CD3 zeta chain may bring the enzyme into close proximity of actin and a possible regulation of actin polymerization through localized production of PtdIns4P and PtdIns(4,5)P2.
Fernandis
Aaron Z
AZ
Biotechnology Group, School of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Srivastava
Rupa
R
Sinha
Ranjeet K
RK
Subrahmanyam
Gosukonda
G
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
D000199:Actins; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; C037178:phosphatidylinositol 4-phosphate; D003208:Concanavalin A; D014443:Tyrosine; D019870:1-Phosphatidylinositol 4-Kinase