16 - Lecture 16 November 5, 2008 A Disintegrin And...

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1 Lecture 16 AD isintegrin A nd M etalloproteinases ( ADAMs ) A Disintegrin A nd M etalloproteinase- T hrombospondin M otifs ( ADAMTSs ) Matrix glycoproteins: the Laminin Family November 5, 2008
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2 (15) Nov 3 MMPs and matrix remodeling (16) Nov 5 ADAMS and Laminins (17) Nov 10 Fibronectin and integrin activation Nov 12 Term test #2: From HA to lecture 14 255 McCaul Street Exam Centre in Room 200 3:10 – 4:30 P.M. (18) Nov 17 Dr. Christopher McCulloch Director of the CIHR Group in Matrix Dynamics University of Toronto “The role of cell adhesions in diabetic cardiomyopathy” (19) Nov 19 SIBLING family of glycoproteins and tissue mineralization (20) Nov 24 SPARC/osteonectin and collagen IV maturation (21) Nov 26 Elastin: tissue elasticity and resilience (22) Dec 1 Neural crest cell migration and ECM guidance cues (23) Dec 3 ECM and cancer progression
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3 MT1-MMP ADAMs ADAM-TS Secreted Plasma membrane- associated PM Structure of MT1-MMP, ADAMS and ADAM-TS A key difference between MMPs and ADAMs is the presence a unique integrin receptor-binding disintegrin domain present in ADAMs Thrombospodin motif Manso et al (2006) Cardiovascular Res 69: 574-584v
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4 Plasma membrane PM ADAMS: essential functions in cell-cell interactions, proteolysis of cytokines and their cognate receptors, growth factors. and other targets Often referred to as sheddases Binds to ECM components (e.g. FN) and integrins ~ 30 ADAMs Manso et al (2006) Cardiovascular Res 69: 574-584v Examples: α 4 β 1 ADAM-28 α 5 β 1 ADAM-15, -17 α 6 β 1 ADAM-9 α 7 β 1 ADAM-12 α 9 β 1 ADAM-12, -15 α V β 3 ADAM-15 α V β 5 ADAM-9
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5 The ADAM uses its disintegrin to bind to the substrate and uses its Zn 2+ containing metalloproteinase active site to cleave the substrate ADAM Substrate e.g., Adam10-/-: Embryonic lethal (E9.5), defective heart
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This note was uploaded on 09/29/2009 for the course CSB csb327 taught by Professor Ringuitte during the Fall '08 term at University of Toronto- Toronto.

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16 - Lecture 16 November 5, 2008 A Disintegrin And...

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