Structural Change in SH2 Domains

Information

  • NSF Award
  • 9304469
Owner
  • Award Id
    9304469
  • Award Effective Date
    9/1/1993 - 30 years ago
  • Award Expiration Date
    2/28/1997 - 27 years ago
  • Award Amount
    $ 255,000.00
  • Award Instrument
    Continuing grant

Structural Change in SH2 Domains

9304469 Shoelson Growth factor/insulin stimulation of the respective tyrosine kinase receptors results in the physical assembly of macromolecular protein complexes at the cytoplasmic surface of the cell membrane. These protein-protein associations are mediated by interactions between phosphoproteins and additional cytoplasmic proteins having Src-homology 2 (SH2) domains (ca.100 residue, modular phosphotyrosine binding pockets). Recently several methods were developed to analyze structure/function relationships between intact phosphoproteins and SH2 domain proteins and truncated versions of both. These findings suggest that phosphoprotein interactions with PI 3-kinase SH2 domains might regulate enzyme function by an allosteric mechanism. This project proposes to extend these observations and determine whether SH2 domain occupancy is a generalized mechanism for regulating catalytic activity. Two members of each SH2 protein class will be analyzed: tyrosine kinases Src & Lck, other enzymes PLC-gamma & SH-PTP, and putative linkers PI 3-kinase p85 & Crk. %%% Many growth factors and related hormones like insulin activate receptors with intrinsic protein tyrosine kinase activity to elicit a wide range of biochemical responses, which ultimately lead to changes in cellular differentiation, metabolism, morphology and proliferation. These studies explore how a class of soluble proteins called SH2 domain proteins contributes to the regulation of signal transduction mediated by these hormones and growth factors. ***

  • Program Officer
    Marcia Steinberg
  • Min Amd Letter Date
    7/15/1993 - 30 years ago
  • Max Amd Letter Date
    5/5/1995 - 29 years ago
  • ARRA Amount

Institutions

  • Name
    Joslin Diabetes Center
  • City
    Boston
  • State
    MA
  • Country
    United States
  • Address
    One Joslin Place
  • Postal Code
    022155397
  • Phone Number
    6173092543

Investigators

  • First Name
    Steven
  • Last Name
    Shoelson
  • Start Date
    9/1/1993 12:00:00 AM

FOA Information

  • Name
    Health
  • Code
    203000
  • Name
    Life Science Biological
  • Code
    61

Program Element

  • Text
    MOLECULAR BIOCHEMISTRY
  • Code
    1166

Program Reference

  • Text
    UNASSIGNED
  • Code
    0
  • Text
    GENERAL FOUNDATIONS OF BIOTECHNOLOGY
  • Code
    9183
  • Text
    BIOTECHNOLOGY
  • Text
    OTHER RESEARCH OR EDUCATION