Sandbox Reserved 1790

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{{BAMBED
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|DATE=June 14, 2016
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|DATE=March 17, 2023
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|BAMBEDDOI=10.1002/bmb.21026
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== Introduction ==
== Introduction ==
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'''Receptor Tyrosine Kinase Receptor'''
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'''SHOC2-PP1C-MRAS''' is a ternary complex formed by the individual proteins: SHOC2, PP1C, and MRAS. Formation of this complex begins with a signal binding to a receptor tyrosine kinase receptor(RTK). This causes membrane bound MRAS to exchange GDP for GTP. From here the complex comes together and is able to dephosphorylate the RAF complex leading to further downstream signaling effects.
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*[[Lipid signaling]]
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*[[Transmembrane (cell surface) receptors]]
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[[Image:LPA_in_membrane4.fw.png|200px|center|thumb|'''Figure 1:''' LPA receptor (blue) bound to the cell membrane. The binding pocket is highlighted in red. The added bRIL protein is highlighted in orange.]]
[[Image:LPA_in_membrane4.fw.png|200px|center|thumb|'''Figure 1:''' LPA receptor (blue) bound to the cell membrane. The binding pocket is highlighted in red. The added bRIL protein is highlighted in orange.]]
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== Lysophosphatidic Acid ==
 
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[[Image:LPA.png|220px|left|thumb|'''Figure 2:''' Chemical Structure of LPA (monoacyl-sn-glycero-3-phosphate)]]
 

Revision as of 17:40, 17 March 2023

This page, as it appeared on March 17, 2023, was featured in this article in the journal Biochemistry and Molecular Biology Education.

Contents

SHOC2-PP1C-MRAS

Introduction

SHOC2-PP1C-MRAS is a ternary complex formed by the individual proteins: SHOC2, PP1C, and MRAS. Formation of this complex begins with a signal binding to a receptor tyrosine kinase receptor(RTK). This causes membrane bound MRAS to exchange GDP for GTP. From here the complex comes together and is able to dephosphorylate the RAF complex leading to further downstream signaling effects.


Figure 1: LPA receptor (blue) bound to the cell membrane. The binding pocket is highlighted in red. The added bRIL protein is highlighted in orange.
Figure 1: LPA receptor (blue) bound to the cell membrane. The binding pocket is highlighted in red. The added bRIL protein is highlighted in orange.



Overall Structure

SHOC2

PP1C

MRAS

Key Ligand Interactions

Figure 3: Electrostatic illustration of the amphipathic binding pocket of the LPA1 receptor. This binding pocket was revealed by cutting away the exterior or the protein. This binding pocket, located in the interior of the protein, has both polar and nonpolar regions. The blue and red coloration highlight the positively and negatively charged regions, respectively, and the white color shows the nonpolar region of the binding pocket.
Figure 3: Electrostatic illustration of the amphipathic binding pocket of the LPA1 receptor. This binding pocket was revealed by cutting away the exterior or the protein. This binding pocket, located in the interior of the protein, has both polar and nonpolar regions. The blue and red coloration highlight the positively and negatively charged regions, respectively, and the white color shows the nonpolar region of the binding pocket.

SHOC2 and PP1C

SHOC2 and MRAS

PP1C and MRAS

Signaling Pathway

Figure 1:Signaling cascade is shown with SHOC2 in pink, PP1C in blue, and MRAs in white.
Figure 1:Signaling cascade is shown with SHOC2 in pink, PP1C in blue, and MRAs in white.
Figure 2:PP1C dephosphorylates RAF protein at serine 259
Figure 2:PP1C dephosphorylates RAF protein at serine 259


Disease Relevance

Cancer

RASopathies

Future Studies

3D structures of lysophosphatidic acid receptor

4z34, 4z35, 4z36 - hLPA1 + antagonist - human
2lq4 – hLPA1 second extracellular loop – NMR
4p0c – hLPA2/NHERF2
5xsz – LPA6A (mutant) – zebra fish

References

[1]. [2]. [3]. [4].

  1. ↑ Hauseman ZJ, Fodor M, Dhembi A, Viscomi J, Egli D, Bleu M, Katz S, Park E, Jang DM, Porter KA, Meili F, Guo H, Kerr G, Molle S, Velez-Vega C, Beyer KS, Galli GG, Maira SM, Stams T, Clark K, Eck MJ, Tordella L, Thoma CR, King DA. Structure of the MRAS-SHOC2-PP1C phosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-05086-1. doi:, 10.1038/s41586-022-05086-1. PMID:35830882 doi:http://dx.doi.org/10.1038/s41586-022-05086-1
  2. ↑ Kwon JJ, Hajian B, Bian Y, Young LC, Amor AJ, Fuller JR, Fraley CV, Sykes AM, So J, Pan J, Baker L, Lee SJ, Wheeler DB, Mayhew DL, Persky NS, Yang X, Root DE, Barsotti AM, Stamford AW, Perry CK, Burgin A, McCormick F, Lemke CT, Hahn WC, Aguirre AJ. Structure-function analysis of the SHOC2-MRAS-PP1C holophosphatase complex. Nature. 2022 Jul 13. pii: 10.1038/s41586-022-04928-2. doi:, 10.1038/s41586-022-04928-2. PMID:35831509 doi:http://dx.doi.org/10.1038/s41586-022-04928-2
  3. ↑ Lavoie H, Therrien M. Structural keys unlock RAS-MAPK cellular signalling pathway. Nature. 2022 Sep;609(7926):248-249. PMID:35970881 doi:10.1038/d41586-022-02189-7
  4. ↑ Liau NPD, Johnson MC, Izadi S, Gerosa L, Hammel M, Bruning JM, Wendorff TJ, Phung W, Hymowitz SG, Sudhamsu J. Structural basis for SHOC2 modulation of RAS signalling. Nature. 2022 Jun 29. pii: 10.1038/s41586-022-04838-3. doi:, 10.1038/s41586-022-04838-3. PMID:35768504 doi:http://dx.doi.org/10.1038/s41586-022-04838-3

Proteopedia Resources

Category:Lysophosphatidic acid binding

Category:Lysophosphatidic acid

Butler University Proteopedia Pages

See also:

</StructureSection>

Student Contributors

Madeline Gilbert Inaya Patel Rushda Hussein

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