Signal Transduction

Signal Transduction - Biochemistry of Metabolism Signal...

Info iconThis preview shows pages 1–12. Sign up to view the full content.

View Full Document Right Arrow Icon
Signal Transduction Copyright © 1999-2008 by Joyce J. Diwan. All rights reserved. Biochemistry of Metabolism
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Many enzymes are regulated by covalent attachment of phosphate , in ester linkage, to the side-chain hydroxyl group of a particular amino acid residue (serine, threonine, or tyrosine). H 3 N + C COO - CH OH CH 3 H threonine (Thr) H 3 N + C COO - CH 2 OH H serine (Ser)
Background image of page 2
A protein kinase transfers the terminal phosphate of ATP to a hydroxyl group on a protein. A protein phosphatase catalyzes removal of the P i by hydrolysis. Protein OH + ATP Protein O P O O - O - + ADP P i H 2 O Protein Kinase Protein Phosphatase
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Phosphorylation may directly alter activity of an enzyme, e.g., by promoting a conformational change. Alternatively, altered activity may result from binding another protein that specifically recognizes a phosphorylated domain. E.g., 14-3-3 proteins bind to domains that include phosphorylated Ser or Thr in the sequence RXXX[pS/pT]XP, where X can be different amino acids. Binding to 14-3-3 is a mechanism by which some proteins (e.g., transcription factors) may be retained in the cytosol, & prevented from entering the nucleus.
Background image of page 4
Protein kinases and phosphatases are themselves regulated by complex signal cascades. For example: Some protein kinases are activated by Ca ++ - calmodulin . Protein Kinase A is activated by cyclic-AMP (cAMP). Protein OH + ATP Protein O P O O - O - + ADP P i H 2 O Protein Kinase Protein Phosphatase
Background image of page 5

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Adenylate Cyclase (Adenylyl Cyclase) catalyzes: ATP cAMP + PP i Binding of certain hormones (e.g., epinephrine) to the outer surface of a cell activates Adenylate Cyclase to form cAMP within the cell. Cyclic AMP is thus considered to be a second messenger . N N N N NH 2 O OH O H H H H 2 C H O P O O- 1' 3' 5' 4' 2' cAMP
Background image of page 6
Phosphodiesterase enzymes catalyze: cAMP + H 2 O AMP The phosphodiesterase that cleaves cAMP is activated by phosphorylation catalyzed by Protein Kinase A. Thus cAMP stimulates its own degradation , leading to rapid turnoff of a cAMP signal. N N N N NH 2 O OH O H H H H 2 C H O P O O- 1' 3' 5' 4' 2' cAMP
Background image of page 7

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Protein Kinase A (cAMP-Dependent Protein Kinase) transfers P i from ATP to OH of a Ser or Thr in a particular 5-amino acid sequence. Protein Kinase A in the resting state is a complex of: 2 catalytic subunits ( C ) 2 regulatory subunits ( R ).
Background image of page 8
Background image of page 9

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Background image of page 10
PDB 1F88 G Protein Signal Cascade Most signal molecules targeted to a cell bind at the cell surface to receptors embedded in the plasma membrane . Only signal molecules able to cross the plasma membrane (e.g., steroid hormones) interact with intracellular receptors. A large family of cell surface receptors have a common structural motif, 7 transmembrane α -helices . Rhodopsin
Background image of page 11

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 12
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 48

Signal Transduction - Biochemistry of Metabolism Signal...

This preview shows document pages 1 - 12. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online