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Unformatted text preview: 10/28/10 Edwin Krebs Edmond Fisher 1 10/28/10 2 10/28/10 1. Kinase cascades 3. Mul0ple func0onality - mul0-func0onal 3. Ac0va0on of some enzymes and inhibi0on of others TH DOPA DDC DBH PNMT 3 10/28/10 Substrate Specificity for Protein Kinases 1. Amino acid specificity 2. Sequence specificity (primary structure) 3. Secondary and Ter0ary Structure 4 10/28/10 4. Spa+al Loca+on in Cell 5 10/28/10 Protein Kinase Ac+va+on (PKA) PS PS Adrenaline 6 10/28/10 Protein Kinase C 1. 2. 3. Ca binding and requirement for ac0vity Phospholipid binding and requirement for ac0vity DAG binding and ac0va0on 7 10/28/10 Ac0va0on mechanism of protein kinase C (C-kinase) A Ac0ve Inac0ve PS, phospha0dyl serine DAG, diacyl glycerol , pseudosubstrate domain C2 C1 The graphic depicts C2 domain of protein kinase C (PKC) beta isoform. Spheres represent calcium cations Ca2+. Scene depicts putative orientation of the domain upon interaction with biological membranes (represented by the plane). The protein fold consists of two sets of beta-pleated sheets (yellow and blue arrows) interconnected by flexible loops. 8 10/28/10 DAG C2 C1 PMA The graphic depicts C1 domain of protein kinase C (PKC) delta isoform. Spheres represent zinc ca0ons which are coordinated by side chain residues and are playing a major role in keeping overall structural stability of the domain. Scene depicts puta0ve orienta0on of the domain upon interac0on with biological membranes (represented by the plane). Depicted in red ball-and-s0ck model is a phorbol-13-acetate - nonphysiological ac0vator of PKC, which increases affinity of the C1 domain towards biological membranes. 9 10/28/10 10 10/28/10 Ca++ Signaling Ion channels Ca-dependent enzymes Ca-dependent kinases Structural proteins Nuclear proteins CALMODULIN endoplasmic 11 10/28/10 some calmodulin-binding proteins with their loca0ons and func0ons 12 10/28/10 13 10/28/10 14 10/28/10 15 10/28/10 Ca/CaM regula0on of Calcium Channels 16 10/28/10 Ac0va0on of CaM Kinase II or IP 3 domain 17 10/28/10 Figure 15-44 Molecular Biology of the Cell ( Garland Science 2008) Figure 15-45 Molecular Biology of the Cell ( Garland Science 2008) 18 ...
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This note was uploaded on 03/28/2011 for the course BIO 317 taught by Professor Simonhalegoua during the Fall '08 term at SUNY Stony Brook.
- Fall '08