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Growth Factor

  1. Complex arrays of intercellular pathways
  2. Autocrine: e.g. Compensated epithelial hyperplasia (Liver Regeneration)
    1. Tumors (GFS & Cytokines)
      1. Paracrine -cause wound healing        
      2. Endocrine
    2. Cell surface receptors: On cell surface
      1. Cytoplasm      
      2. Nucleus
Receptor with intrinsic Tyrosine Kinase activity:-
GF (EGF, PDGF, FGF) 7 spanning receptor
  1. Receptors with intrinsic tyrosine kinase activity
    1. Ras
    2. IP3 Pathway           
    3. PI3 Kinase  
    4. Src family
  2. Without intrinsic catalytic activity
    Functional response, not proliferation: cytokine receptor super family
  3. G-Protein linked: for inflammatory chemokine & hormones

Signal Transduction System


MAP - Kinase pathway: ras protein [GTPase family] binds to a Ras causes activation of → Raf → further increases MEK → leads to↑ C-jun & ↑ C- fos gets activated                         

Net result: activation of protein phosphorylation cascade - amplifies signal; stimulates quiescent cells to enter growth cycle.


A. Transcription Factors

Regulatory domain Activation domain - cmyc

Repression domain - p53, Rb-1


B. Cell Cycle Regulators

  1. Molecular controls:
    1. Cascade of protein phosphorylation pathways (group of proteins called cyclins)
    2. Set of Checkpoints
  2. Cyclins & CDKs (CDKs constitutively expressed) After completion of function: Cyclins → degraded by ubiquitin- proteasome pathway Check points: Surveillance mechanism Q
  3. Sense problems in DNA replication, repair, segregation (e.g., p53, p21)

C. Growth Inhibition:

  1. Contact inhibition
  2. Growth suppression

e.g. TGF-ß CDK - (via SMAPs)


D. Growth Factors:

  1. Effect on growth, locomotion, differentiation, contraction
  2. Non specific / specific
  3. EGF: binds to receptor (c-erb B1) with T. K. activity
    Mitogen for epithelial cells, fibroblasts, hepatocytes
    TGF a binds to EGF receptor, function is similar to EGF
  4. PDGF: Dimers of A & B chain's
    Stored in platelet ex: granules
    Causes migration & proliferation of fibroblasts, smooth muscle cells, monocytes
  5. EGF: aFGF/FGF-1 (acidic) Bind to receptors with intrinsic T.K. activity
            bFGF/FGF - 2 (basic)
Table: Growth Factors and Cytokines Affecting various steps in wound
1. Monocyte chemotaxis PDGF, FGF, TGF-Beta
2. Fibroblast migration PDGF, EGF, FGF, TGF-beta, TGF, IL-1
3. Fibroblast proliferation PDGF, EGF, FGF, TNF
4. Angiogenesis VEGF, Ang, FGF
5. Collagen synthesis TGF-beta, PDGF
6. Collagenase secretion PDGF, FGF, EGF, TNF, TGF-beta inhibits

E. Function:

  1. Angiogenesis (bFGF)                                                 
  2. Wound Repair
  3. Skeletal muscle development & lung maturation      
  4. Hematopoiesis
  5. VEGF: / Vascular permeability Factor
    (VEGF, VEGE-B, VEGF-C, Placental GF)
    1. Role in vasculogenesis & Angiogenesis
    2. In Ca, chronic inflammation, wound healing
      VEGF- C: Hyperplasia of lymphatic vasculature
  6. TGFß3major isoforms

Family TGF-ß1, TGF ß2, TGF ß3: Bone morphogenetic protein, activins, inhibins, mullerian inhibiting, substance.


TGF-ß1: most widespread

  1. Absent in epithelial cells
  2. Present on fibroblasts & smooth muscle cells:
  3. Low Concentration → + ( synthesis & Sec. of PDGF)
  4. High Concentration → - (exp. Of PDGF receptor)
  5. Stimulates fibroblasts chemotaxis, production of collagen & fibronectin
  6. Reduce collagen degradation

 7. Cytokines


 8. Angio proteins



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