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Fatty acyl chain-dependent but charge-independent association of the SH4 domain of Lck with lipid membranes

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Abstract

The SH4 domain of Src family of nonreceptor protein tyrosine kinases represents the extreme N-terminal 1–16 amino acid region which mediates membrane association of these proteins and facilitates their functions. The SH4 domains among Src members lack well-defined sequence consensus and vary in the net charge. However, they readily anchor to the cytoplasmic face of the plasma membrane upon fatty acid acylation. Here, we report the membrane association of differentially acylated SH4 domain of Lck kinase, which has net negative charge at physiological pH. Our results suggest that despite the net negative charge, the SH4 domain of Lck associates with membranes upon fatty acid acylation. While myristoylation at the N-terminus is sufficient for providing membrane anchorage, multiple acylation determines orientation of the peptide chain with respect to the lipid bilayer. Hence, fatty acylation serves more than just a lipid anchor. It has an important role in regulating the spatial orientation of the peptide domain with respect to the lipid bilayer, which could be important for the interaction of the other domains of these kinases with their partners.

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Acknowledgements

RN is recipient of JC Bose fellowship from the Department of Science and Technology, India.

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Author notes

  1. Avaronnan Harishchandran

    Present address: Novozymes South Asia Pvt Ltd, Plot No. 32, 47-50, EPIP Area, Whitefield, Bangalore, 560 066, India

Authors and Affiliations

  1. CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India

    Anoop Rawat, Avaronnan Harishchandran & Ramakrishnan Nagaraj

Authors
  1. Anoop Rawat
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  2. Avaronnan Harishchandran
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  3. Ramakrishnan Nagaraj
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Corresponding author

Correspondence to Ramakrishnan Nagaraj.

Additional information

MS received 08 August 2012; accepted 25 October 2012

Corresponding editor: Anand Kumar Bachhawat

[Rawat A, Harishchandran A and Nagaraj R 2013 Fatty acyl chain-dependent but charge-independent association of the SH4 domain of Lck with lipid membranes. J. Biosci. 38 1–9] DOI 10.1007/s12038-012-9288-1

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Rawat, A., Harishchandran, A. & Nagaraj, R. Fatty acyl chain-dependent but charge-independent association of the SH4 domain of Lck with lipid membranes. J Biosci 38, 63–71 (2013). https://doi.org/10.1007/s12038-012-9288-1

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  • DOI: https://doi.org/10.1007/s12038-012-9288-1

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