Presentation is loading. Please wait.

Presentation is loading. Please wait.

SIG Projects Suggested Project Idea: Model recruitment of signaling proteins (with SH2 domains) to a receptor tyrosine kinase (RTK) in different cell.

Published byHolly Knight Modified over 6 years ago

Similar presentations

Presentation on theme: "SIG Projects Suggested Project Idea: Model recruitment of signaling proteins (with SH2 domains) to a receptor tyrosine kinase (RTK) in different cell."— Presentation transcript:

1 SIG Projects Suggested Project Idea: Model recruitment of signaling proteins (with SH2 domains) to a receptor tyrosine kinase (RTK) in different cell lines Mentor: Bill Hlavacek

2 RTKs (2 out of 3 tyrosine kinases in human genome)

3 Mechanisms of activation

4 GRB2 2885 P62993 FGFR3 Y724 2261 P22607 KPANCTHDLyMIMRECW FLT1 Y1213 2321 P17948 NSGSSDDVRyVNAFKFM INSR Y1011 3643 P06213 ASDVFPCSVyVPDEWEV KIT Y936 3815 P10721 QISESTNHIySNLANCS MET Y1313 4233 P08581 QPEYCPDPLyEVMLKCW Y1356 EHYVHVNATyVNVKCVA MST1R Y1317 4486 Q04912 QPEYCPDSLyQVMQQCW RET Y1096 5979 P07949 FPRYPNDSVyANWMLSP TEK Y1113 7010 Q02763 NTTLYEKFTyAGIDCSA FRS2 Y196 10818 Q8WU20 LVAEEQVHTyVNTTGVQ EGFR Y1092 1956 P00533 DDTFLPVPEyINQSVPK Y1138 HSTAVGNPEyLNTVQPT

5 Protein copy numbers vary from cell type to cell type

6 Absolute quantification of protein abundances in HeLa Kyoto cells

7 Predicted levels of recruitment to EGFR based on measured KD’s and protein copy numbers for HeLa S3 cells

8 Variability in (predicted) recruitment across cell lines
Kulak et al Geiger et al HeLa A549 GAMG HEK293 HepG2 Jurkat K562 LnCap MCF7 RKO U2OS SHC1 SRC GRB2 LCK PLCG1 RASA1 YES1 GRAP2 SH2B3 PTPN11* PTPN11 VAV2 SOCS6 SH2D2A* SRC* SLA2 VAV2** PIK3R2 PIK3R1 YES1** VAV3 PIK3R3 SH2D2A VAV1* PIK3R1** PIK3R2* SH2B2 GRB7 PIK3R1*** VAV2* PTK6 PIK3R2*** SH2B3*** SHB PIK3R2** VAV3*** VAV3* VAV1*** PIK3R3** VAV1 BLK SHB* PLCG1** TEC SLA2*** VAV2*** HSH2D

9 Suggested steps Pick an RTK (don’t pick EGFR, IGF1R, or TrkA)
Develop a simple model for RTK dimerization by ligand ID sites of autophosphorylation in RTK Find KD’s for these sites and SH2/PTB domains Find protein copy number measurements for RTK binding partners for multiple cell lines Add autophosphorylation to model Add recruitment of SH2/PTB domain-containing proteins to pY’s Predict relative levels of recruitment for different cell lines

10 Questions? E-mail: wshlavacek@gmail.com or wish@lanl.gov
iPhone:

Download ppt "SIG Projects Suggested Project Idea: Model recruitment of signaling proteins (with SH2 domains) to a receptor tyrosine kinase (RTK) in different cell."

Similar presentations

Signal Transduction Mechanisms Underlying Underlying Growth Control and Oncogenesis Ronit Sagi-Eisenberg Dept. of Cell and Developmental Biology Sackler.

Signal Transduction Mechanisms Underlying Underlying Growth Control and Oncogenesis Ronit Sagi-Eisenberg Dept. of Cell and Developmental Biology Sackler.
BioNetGen: a system for modeling the dynamics of protein-protein interactions Bill Hlavacek Theoretical Biology and Biophysics Group Los Alamos National.

BioNetGen: a system for modeling the dynamics of protein-protein interactions Bill Hlavacek Theoretical Biology and Biophysics Group Los Alamos National.
Lecture 23 Signal Transduction 2

Lecture 23 Signal Transduction 2
Cell Signaling Lecture 10.

Cell Signaling Lecture 10.
Ligand Receptor Cortisol Receptor is located in the cytosol Retinoid Receptors are in the nucleus Target gene in the nucleus Regulation of Transcription.

Ligand Receptor Cortisol Receptor is located in the cytosol Retinoid Receptors are in the nucleus Target gene in the nucleus Regulation of Transcription.
Signal Transduction II Transduction Proteins & Second Messengers.

Signal Transduction II Transduction Proteins & Second Messengers.
Example RTK: EGF receptor

Example RTK: EGF receptor
Underlying Principles and Future Targets for Molecular Therapy of SCCHN Prof. Tim H. Brümmendorf Dept. of Hematology and Oncology University Hospital Eppendorf.

Underlying Principles and Future Targets for Molecular Therapy of SCCHN Prof. Tim H. Brümmendorf Dept. of Hematology and Oncology University Hospital Eppendorf.
Protein Domains That Interact with Receptor Tyrosine Kinases: Structural Aspects Ming-Ming Zhou, Ph.D. MSSM Department of Pharmacology Course on “Cell.

Protein Domains That Interact with Receptor Tyrosine Kinases: Structural Aspects Ming-Ming Zhou, Ph.D. MSSM Department of Pharmacology Course on “Cell.
Overview of Targeted Therapy Mechanisms November 11, 2011 Targeted Therapies and Biological Therapies SIG.

Overview of Targeted Therapy Mechanisms November 11, 2011 Targeted Therapies and Biological Therapies SIG.
Graphical Rule-Based Modeling of Signal-Transduction Systems

Graphical Rule-Based Modeling of Signal-Transduction Systems
Chapter 11 Cell Communication Dr. Joseph Silver. this chapter deals with - how cells receive messages - what changes take place in the cell - and what.

Chapter 11 Cell Communication Dr. Joseph Silver. this chapter deals with - how cells receive messages - what changes take place in the cell - and what.
Tyrosine Kinases as Targets for Cancer Therapy Krause DS, Van Etten RA N Engl J Med 2005;353(2):172-87. Krause DS, Van Etten RA N Engl J Med 2005;353(2):172-87.

Tyrosine Kinases as Targets for Cancer Therapy Krause DS, Van Etten RA N Engl J Med 2005;353(2): Krause DS, Van Etten RA N Engl J Med 2005;353(2):
Transduction of Extracellular Signals Specific receptors in plasma membranes respond to external chemicals (ligands) that cannot cross the membrane: hormones,

Transduction of Extracellular Signals Specific receptors in plasma membranes respond to external chemicals (ligands) that cannot cross the membrane: hormones,
Date of download: 9/17/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved. Schematic comparison of structural features of cell surface growth.

Date of download: 9/17/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved. Schematic comparison of structural features of cell surface growth.
Medical School of Qingdao University

Medical School of Qingdao University
The JAK-STAT signaling system represents a series of reactions that take place when a hormone binds a receptor that uses this system. While the hormone.

The JAK-STAT signaling system represents a series of reactions that take place when a hormone binds a receptor that uses this system. While the hormone.
Figure 1. Resistance mechanism against first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). (A) Mutations in the EGFR.

Figure 1. Resistance mechanism against first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). (A) Mutations in the EGFR.
Schematic comparison of structural features of cell surface growth factor receptor tyrosine kinases and membrane-associated tyrosine kinase oncogene products.

Schematic comparison of structural features of cell surface growth factor receptor tyrosine kinases and membrane-associated tyrosine kinase oncogene products.
Intercellular Communication

Intercellular Communication

Similar presentations

Ads by Google