Lecture 12 MMPs Nov 14, 2016

Lecture 12 MMPs Nov 14, 2016 - Lec 11 Nov 2 Regulation of...

Info icon This preview shows pages 1–8. Sign up to view the full content.

View Full Document Right Arrow Icon
1 Lec 11 Nov 2 Regulation of cell adhesion and migration: integrins, actinomyosin contractions, Rho GTPases and fibronectin Regulation of cell adhesion and migration continued: Focal adhesion kinase, syndecan-4 Lecture 12 Nov 14 Matrix Remodeling Metalloproteinases
Image of page 1

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

View Full Document Right Arrow Icon
2 Matrix Metalloproteinases (MMPs) Substrate specificity Structural organization of secreted MMPs Activation of MMPs Tissue Inhibitors of MMPs Membrane-Type MMPs (MT-MMPs) Role of MT1-MMP in cancer cell invasion ADAMS: structural organization, substrate specificity and function
Image of page 2
Secreted Pro-MMPs MMPs Plasminogen Plasmin Serine proteases :Urokinase-plasminogen activator (uPA); Tissue-plasminogen activatior (tPA) In addition to activating MMPs, plasmin can act on fibrin, collagens, fibronectin and proteoglycans Pro-uPA uPA Pro-tPA tPA L Cathepsins: cysteine proteases in lysosomes (L) (terminal degradation) – also secreted and associated the the PM MT-MMPs ADAMs ADAM-TSs ECM remodeling/degrading enzymes ADAM: A disintegrin and metaproteinase; ADAM-TS, ADAM with at least on thrombospondin (TS) repeat MT-MMP ; Membrane-Type MMP; activated intracellular by furins in the trans-golgi network Aminopeptidases (ANPs); exopeptidases ECM
Image of page 3

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

View Full Document Right Arrow Icon
4 MMP substrates identified in complex biological samples by proteomic analysis: Degradomics Rodriguez et al. 2009. Biochem Biophys Acta., in press. MMP substrates identified using a variety of proteomic techniques Proteins identified in protoemic screens that were biochemically validated as MMP substrates MMPs are also called matrixins
Image of page 4
5 Pro-MMP-2 and MMP-9 (Secreted) Pre-peptide Pro-domain ~ 170 a.a. Cysteine switch Hemopexin Domain ~200 a.a. FN Type II repeats Hinge Region/ Linker region Catalytic Domain ~170 a.a. Cys-Zn2+ interactions Substrate specificity FN type II domain is essential for gelatinases to effectively cleave elastin, gelatins and type IV collagen The Hemopexin domain is essential for collagenolytic activity of collagenases. Latent proform First MMP discovered in 1962
Image of page 5

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

View Full Document Right Arrow Icon
6 Matrix Metalloproteinases (MMPs) Substrate specificity Structural organization of secreted MMPs Activation of MMPs Tissue Inhibitors of MMPs Membrane-Type MMPs (MT-MMPs) Role of MT1-MMP in cancer cell invasion ADAMS: structural organization, substrate specificity and function
Image of page 6
7 C Zn ++ Catalytic domain Pro-domain In inactive proMMPs, the SH group of a cysteine residue in the prodomain interacts with the catalytic zinc ion in the catalytic domain.
Image of page 7

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

View Full Document Right Arrow Icon
Image of page 8
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern