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Type II PtdIns 4-kinase β associates with CD4–p56lck complex and is involved in CD4 receptor signaling

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Abstract

Type II phosphatidylinositol (PtdIns) 4-kinases are involved in the synthesis of PtdIns 4-phosphates and modulate various cell functions like, intracellular signaling, cytoskeletal rearrangements, vesicular trafficking, and pathogen invasion. In CD3 receptor activated T cells, a type II PtdIns 4-kinase β is recruited to CD3 receptor zeta and plays a role in intracellular calcium release and probably in actin cytoskeleton reorganization. T cell receptor mediated activation is supported by CD4 receptor. The role of type II PtdIns 4-kinase β in CD4 receptor-mediated signaling was addressed in the present manuscript. Crosslinking of CD4 receptors with monoclonal antibodies showed an increase in CD4-associated PtdIns 4-kinase activity and requires p56lck activity. Biochemical characterization suggests that it belongs to type II PtdIns 4-kinase family. shRNA mediated knockdown of type II PtdIns 4-kinase β showed abrogation of CD4 receptor induced intracellular calcium release. These results suggest that type II PtdIns 4-kinase β plays an integral part in CD4 receptor-mediated signaling.

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Acknowledgments

Funding from Council of Scientific and Industrial Research, Govt. of India, grants (37(0994)/98/EMR-II, 37(1099)/02/EMR-II) to Dr. G. Subrahmanyam and a fellowship to Ranjeet K. Sinha was gratefully acknowledged. The authors declare that the funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Dr. S.V. Chiplunkar and Dr. Dakshayani Rao for providing facility and key assistance in calcium assay.

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Authors and Affiliations

  1. Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai, 400076, India

    Ranjeet Kumar Sinha, Naveen Bojjireddy & Gosukonda Subrahmanyam

  2. Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, 410210, India

    Deepak Kanojia

  3. Molecular and Experimental Medicine, The Scripps Research Institute, 92037, La Jolla, CA, USA

    Ranjeet Kumar Sinha

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  1. Ranjeet Kumar Sinha
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Correspondence to Ranjeet Kumar Sinha.

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Sinha, R.K., Bojjireddy, N., Kanojia, D. et al. Type II PtdIns 4-kinase β associates with CD4–p56lck complex and is involved in CD4 receptor signaling. Mol Cell Biochem 395, 231–239 (2014). https://doi.org/10.1007/s11010-014-2129-9

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